Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication ALIMTA ® is a folate analog metabolic inhibitor indicated: in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. ( 1.1 ) in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous NSCLC. FDA label
Also known as Pemetrexed - Phase 1, LY231514, Pemetrexed - Phase 2, pemetrexed
ALIMTA · 98 trials · 79 indications
OS is defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. OS was estimated using the Kaplan-Meier method.
OS was defined as the duration from date of randomization to date of death from any cause. Participants who were alive were censored at the date of last contact.
PFS was defined as the time from date of randomization to the objective disease progression or death due to any cause. Response was defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. Progressive disease (PD) was defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions. Participants who did not have a complete baseline disease assessment were censored at the date of randomization, regardless if PD was objectively determined or if participant died or if a participant was not known to have died or have objective PD at the data inclusion cutoff date. PFS was censored at the last complete objective progression-free disease assessment date.
G4PFS was defined as the duration from the date of randomization to the earliest occurrence date of one of the following three events: Common Terminology Criteria (CTC) grade 4 adverse events (G4AEs), or progressive disease (PD) or death from any cause, whichever occurred earlier. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who had no G4AEs, or PD, or death at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy.
Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive.
Investigator-assessed objective PFS was measured from the date of randomization to the first date of objectively determined progressive disease (PD) or death from any cause. For patients not known to have died as of the data cutoff date and who did not have objective PD, PFS was censored at the date of last objective tumor assessment. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD = 20% increase in sum of longest diameter of target lesions.
Defined as the time from date of randomization to first date of a Grade 3 or 4 treatment-emergent adverse event (TEAE; as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events \[CTCAE\], version 3.0) or death due to any cause. Grade 3 TEAE: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4 TEAE: Life-threatening consequences; urgent intervention indicated. Participants who were alive without experiencing Grade 3 or 4 toxicity were censored at the date of last contact.
PFS time was the elapsed time from the date of randomization to the first date of objective progression of disease or death from any cause. PFS was censored at the date of the participant's last tumor assessment for participants who were not known to have died or to have PD as of the data-inclusion cut-off date for analysis. PD, defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0), was at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
Number of events of brain or central nervous system (CNS) bleeding
Best overall Prostate-Specific Antigen (PSA) response PSA response is defined by a greater than or equal to 50% decline in PSA confirmed by a second PSA value at least 4 weeks after the first PSA response timepoint PSA Stable Disease is defined as less than a 50% decline in PSA and less than a 50% increase in PSA from baseline PSA progression is defined as greater than or equal to a 50% increase in PSA compared to baseline
Overall response rate is the percentage of patients with complete response or partial response per RECIST v.1 Criteria. Complete response (CR) = Disappearance of all target lesions, disappearance of all nontarget lesions for at least 4 weeks. Partial Response (PR) = At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters.
The percentage of patients who were alive at 3 years from time of first study treatment until date of death from any cause. Overall survival is shown for the Intent-to-Treat population.
Participants were considered adherent from the time of the first dose in Cycle 1 (hospital administration) until either the last day of the cycle when the participant reverted to pemetrexed hospital administration or the last day of the cycle when the participant discontinued study treatment or the study for reasons related to the home setting. The percentage of participants who adhered to treatment administration at home was estimated by a Kaplan-Meier survival analyses approach. Participants who died or discontinued the study and treatment without reverting to hospital administration were censored at the time of discontinuation.
PFS was defined as the time from date of randomization until the date of disease progression, or death from any cause, whichever was first. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. Participants without documentation for disease progression or death were censored at the date of last tumor assessment. The PFS was estimated following the Kaplan-Meier method.
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size \[\<10 millimeter (mm) short axis\]. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameters. ORR calculated as: (sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100.
Progression free survival (PFS) was defined as the time from study enrollment to the first observation of progressive disease (PD) or death from any cause. For participants not known to have died as of the data cut-off date and who did not have objective PD, PFS was censored at the date of the last objective progression-free disease assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study drug) prior to objectively determined PD or death, PFS was censored at the date of the last objective progression-free disease assessment prior to start of postdiscontinuation chemotherapy. If a participant did not have a complete baseline disease assessment, then PFS was censored at the enrollment date, regardless whether or not objectively determined PD or death had been observed for the participant.
Progression-Free Survival (PFS) is defined as the time from the date of study enrollment to the first date of objectively determined PD or death from any cause. PD is defined using Response Evaluation Criteria in Solid Tumours (RECIST) Guidelines (Version 1.0), as at least a 20% increase in the sum of longest diameter (LD) of target lesions, taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last objective progression-free disease assessment. For participants who receive subsequent systemic anticancer therapy, PFS will be censored at the date of the last objective progression-free disease assessment prior to post-discontinuation systemic therapy.
Response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions. Tumor response is presented as a percentage (%) and is the number of participants with a CR plus PR divided by the number of participants in the protocol qualified (PQ) population, then multiplied by 100.
Results are presented for the number of participants with drug-related Grade 3 or 4 toxicity/adverse event (AE). Grades range from 0 (none) to 5 (death), with Grade 3 and 4 being defined as follows: Grade 0 = No AE; Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. A detailed list of Serious and non-serious adverse events is provided in the Reported Adverse Event section.
Progression free survival is defined as the time from randomization until the date of progression of disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is ≥20% increase in sum of longest diameter of target lesions. PD in maintenance phase uses the last lesion assessment prior to randomization as the baseline assessment.
Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response = disappearance of all target lesions. Partial Response = 30% decrease in sum of longest diameter of target lesions. Response rate (percent \[%\])= (number of participants with complete response (CR) or partial response (PR) in stratum/number of participants in stratum)\*100.
Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) = at least a 20% increase in sum of longest diameter of target lesions; Stable Disease (SD) = small changes that do not meet above criteria. Tumor Response Rate(%) = sum of number of PR + CR observed/number of participants qualified for tumor response analysis \* 100.
Time to Progression (TTP) is defined as the interval between the date of treatment initiation and the date of progressive disease. Progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or unequivocal progression of non-target lesions or the appearance of one or more new lesions.
Any untoward medical occurrence in a patient who received study drug was considered an adverse event (AE), without regard to possibility of causal relationship. Treatment-emergent adverse events (TEAE): those which occurred or worsened after baseline. An adverse event resulting in any of the following outcomes, or deemed to be significant for any other reason, was considered to be a serious adverse event (SAE): death; initial or prolonged inpatient hospitalization; a life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Tumor responder is defined as participants exhibiting a best overall study response of complete response (CR; disappearance of all target lesions) or partial response (PR; 30% decrease in sum of longest diameter of target lesions). Non-responders are those who did not meet the above criteria.
For this study, we used the exponential distribution (assumption done for the calculation of the sample size) to estimate the PFS rate. The PFS rate (%) and the 95% confidence intervals were calculated based on the following formula: exp(-6 λ) ± 1.96 \* exp(-6 λ) \* (-6 λ)/√r. Where λ was calculated based on the Maximum-Likelihood estimator for ln(λ) as given by (Collett 2003): ln(λ) = ln\[ r / ∑ti \] with r = number of patients with events up to 6 months, ti = survival time of patient i (i=1,…,n), event or censored up to 6 months, and n= total number of patients per treatment group.
Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve ("respond"), stay the same ("stable"), or worsen ("progression") during treatment. Complete response (CR) = disappearance of all target lesions; Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions; Stable disease (SD) = small changes that do not meet above criteria.
Tumor response is defined as the percentage of patients with either a complete response or a partial response. Response was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions and Partial Response=30% decrease in sum of longest diameter of target lesions.
Participants with best overall response determined from complete response (CR) or partial response (PR) according to Response Criteria in Solid Tumors (RECIST) criteria. For CR or PR, best response must be confirmed. A second assessment performed at 28 days. Two determinations of CR before progression required for rate to=CR. Evaluations include: CR=Disappearance of lesions. PR=≥30% size decrease of lesions. Progressive Disease (PD)=≥20% size increase of lesions. Stable Disease (SD)=Not enough shrinkage for PR nor enough increase for PD. Overall Response Rate=PR+CR/Qualified Participants\*100.
Feasibility was defined as the ability to receive the total planned dose of Pemetrexed administered over a period of no more than 9 weeks permitting scheduling conflict. A ±5 percent variance in the calculated total dose was allowed.
Feasibility was measured by completion of 4 treatment cycles without remaining toxicities \>=Grade 3 at 30 days after last infusion.
TTP was calculated from treatment initiation to disease progression or last follow-up.
pathological assessment of tissue removed during surgery to determine if tumor tissue is still present after chemotherapy
Molecular markers assessed by immunohistochemistry: thymidylate synthase, glycinamide ribonucleotide formyl transferase (GARFT), epidermal growth factor receptor (EGFR); and by polymerase chain reaction: dihydrofolate reductase (DHFR), dihydropyrimidine dehydrogenase (DPD), folylpolyglutamate synthetase (FPGS), reduced folate carrier, alpha folate receptor, Excision Repair Cross-Complementation Group 1 (ERCC1), folylpolyglutamate hydrolase (FPGH). Hypermethylated genes assessed by methylation-specific polymerase chain reaction. Due to small sample size, tumor-tissue analyses were not done.
Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve ("respond"), stay the same ("stable"), or worsen ("progression") during treatment.
Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria as determined by the Case Judgment Committee. Best overall response was defined as the most favorable overall response recorded for each patient during the observation period. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria.
Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve ("respond"), stay the same ("stable"), or worsen ("progression") during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria.
Number of participants with results of pathological review that indicated a complete response. Pathological complete response should be evaluated at the time of surgery (Extrapleural Pneumonectomy \[EPP\]). Resected tissue or pleural fluid should be sent for pathological and histological evaluation.
duration of time from start of treatment until objective tumor progression or withdrawal
rate of radiographic imaging alterations following treatment
The recommended phase II dose. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g.,meningitis) or other grade 4 toxicity.
The incidence of treatment-related adverse events were measured for determining tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). Events of grade 3-5 are defined as moderate and severe adverse events.
Progression-free survival (PFS) time is defined as the time from the date of randomization to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates.
The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after pemetrexed and cisplatin was based on the maximum tolerated dose (MTD) and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity \[AUC(0-∞)\] \>21,000 nanogram\*hour/milliliter \[ng\*h/mL\] and maximum LY2603618 plasma concentration \[Cmax\] \>2000 nanograms/milliliter \[ng/mL\]).
MTD was defined as a dose at which the occurrence of at least 2 dose-limiting toxicities (DLTs) was observed. DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course, including a 2-week recovery period following completion of RT: Grade 4 neutropenia (\<0.5 x 10\^9 cells per liter) lasting \>7 days, febrile neutropenia; ≥Grade 3 neutropenia with fever \>38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations) and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis).
MTD was defined as a dose at which the occurrence of at least 2 dose-limiting toxicities (DLTs) was observed. DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course, including a 2-week recovery period following completion of RT: Grade 4 neutropenia (\<0.5 x 10\^9 cells per liter) lasting \>7 days, febrile neutropenia; ≥Grade 3 neutropenia with fever \>38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations) and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis).
Recommended Phase 2 MTD was highest dose at which no more than 1 of 6 participants experienced dose level toxicity (DLT). DLT=(1) Grade 3/4 dysphagia/esophagitis, leukopenia, thrombocytopenia, febrile neutropenia, fatigue/malaise, pneumonitis, dermatitis, persistent elevation of bilirubin/alkaline phosphatase/aspartate aminotransferase only if resulting in delay of radiotherapy \>1 week, delay of pemetrexed/cisplatin Cycle 2 \>2 weeks, or delay of pemetrexed/cisplatin Cycle 3 past 5 weeks after radiotherapy; (2) other Grade 3 or 4 toxicity possibly related to concurrent treatment administration.
OS was defined as the time from date of enrollment to death due to any cause.
MTD was to be determined by increasing doses of pemetrexed up to 900 mg/m\^2 and carboplatin Area Under the Concentration-Time Curve (AUC) up to 6 mg/mL\*min based on observed pattern of dose limiting toxicity (DLT). See Outcome #3 for DLT. If none of 3 initial participants at a given level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. If at least 2 participants experienced a DLT in Cycle 1 at a dose level, that dose level was considered the MTD. However, based on results from a different Phase 2 Study (NCT00109096), further dose escalations were not explored.
Response is defined as CR (Complete Response) or PR (Partial Response) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions. Response rate (%) = (number of patients with CR+PR/number of patients in Phase 2)\*100
Tumor response was assessed using radiological imaging, which was repeated every 6 weeks prior to every other cycle. Confirmation of response was to occur no less than 4 weeks (28 days) after the first evidence of response.
Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria.
| Arm | Type | Description |
|---|---|---|
| Necitumumab + Pemetrexed + Cisplatin | EXPERIMENTAL | Necitumumab + Pemetrexed + Cisplatin |
| Pemetrexed + Cisplatin | ACTIVE_COMPARATOR | Pemetrexed + Cisplatin |
| Pemetrexed plus Cisplatin | EXPERIMENTAL | - |
| Gemcitabine plus Cisplatin | ACTIVE_COMPARATOR | - |
| Pemetrexed + Cisplatin + Gefitinib | EXPERIMENTAL | - |
| Gefitinib | ACTIVE_COMPARATOR | - |
| Pemetrexed + Carboplatin + Pemetrexed | EXPERIMENTAL | Pemetrexed and Carboplatin followed by Pemetrexed |
| Paclitaxel + Carboplatin + Bevacizumab | ACTIVE_COMPARATOR | Paclitaxel, Carboplatin, and Bevacizumab followed by Bevacizumab |
| Pem/Carbo/Bev | EXPERIMENTAL | Pemetrexed (Pem), carboplatin (Carbo) and bevacizumab (Bev) followed by pemetrexed and bevacizumab |
| Pac/Carbo/Bev | ACTIVE_COMPARATOR | Paclitaxel (Pac), carboplatin (Carbo) and bevacizumab (Bev) followed by bevacizumab |
| pemetrexed + cisplatin followed by pemetrexed | EXPERIMENTAL | pemetrexed plus cisplatin followed by pemetrexed plus best supportive care |
| pemetrexed + cisplatin followed by placebo | PLACEBO_COMPARATOR | pemetrexed plus cisplatin followed by placebo plus best supportive care |
| Arm A: Pemetrexed + Cisplatin and TRT | EXPERIMENTAL | Participants were treated with Pemetrexed plus Cisplatin and concurrent thoracic radiation therapy (TRT) ("Concurrent Phase") for three 21-day cycles, followed by a 3-5 week "Recovery Period," then treated with consolidation chemotherapy with pemetrexed ("Consolidation Phase") for up to four 21-day cycles Concurrent Phase: Pemetrexed: 500 milligrams per meter squared (mg/m\^2), intravenous (IV) on Day 1 of each 21-day cycle for 3 cycles. Cisplatin: 75 mg/m\^2, IV on Day 1 of each 21-day cycle x 3 cycles. TRT: Beginning on Day 1 of chemotherapy, once daily fractions (2 Gray \[Gy\] per day), 5 days a week for 6 weeks and 3 days to target 66 Gy in 33 fractions. Consolidation Phase: Pemetrexed: 500 mg/m\^2, IV on Day 1 of each 21-day cycle up to 4 cycles |
| Arm B: Etoposide + Cisplatin and TRT | ACTIVE_COMPARATOR | Participants were treated with Etoposide plus Cisplatin and concurrent TRT ("Concurrent Phase") for two 28-day cycles, followed by a 3-5 week "Recovery Period," then received consolidation treatment with cytotoxic chemotherapy of choice ("Consolidation Phase") for up to 2 cycles Concurrent Phase: Etoposide/Cisplatin (28-day cycle); Etoposide: 50 mg/m\^2, IV on Days 1 to 5 and Days 29 to 33 and Cisplatin: 50 mg/m\^2, IV on Days1, 8, 29, and 36 Consolidation Phase options: Option 1: Continue the same treatment plan as Concurrent Phase Option 2: Vinorelbine/Cisplatin (21-day cycle); Vinorelbine: 30 mg/m\^2, IV on Days 1, 8, 22, and 29; Cisplatin: 75 mg/m\^2, IV on Days 1 and 22 Option 3: Paclitaxel/Carboplatin (21-day cycle); Paclitaxel: 200 mg/m\^2, IV, on Days 1 and 22; Carboplatin: area under the concentration-time curve (AUC) = 6 (Carboplatin dosing based on calculated creatinine clearance), IV on Days 1 and 22 |
| pemetrexed plus carboplatin | EXPERIMENTAL | Drug: pemetrexed 500 milligrams per square meter (mg/m\^2), intravenous (IV), every (q) 21 days x 6 cycles maximum Drug: carboplatin Area Under the Curve (AUC) 5 milligram\*minute/milliLiter (mg\*min/mL), IV, q 21 days x 6 cycles maximum |
| docetaxel plus carboplatin | ACTIVE_COMPARATOR | Drug: docetaxel 75 mg/m\^2, IV, q 21 days x 6 cycles maximum Drug: carboplatin AUC 5 mg\*min/mL, IV, q 21 days x 6 cycles maximum |
| Pemetrexed/Cisplatin | EXPERIMENTAL | Pemetrexed 500 milligrams per meter square (mg/m\^2) administered intravenously (IV) plus cisplatin 75 mg/m\^2 IV on Day 1 every 21 days. Pretreatment, Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment. Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose. Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose. |
| Placebo/Cisplatin | PLACEBO_COMPARATOR | Placebo (approximately 100 mL normal saline) administered intravenously (IV) plus cisplatin 75 mg/m\^2 on Day 1 every 21 days. Pretreatment - Both Treatment Arms: Dexamethasone administered orally (po): 4 milligrams (mg) twice daily (BID) taken on the day before, the day of, and day after study treatment. Vitamin B12 administered intramuscularly (im): 1000 micrograms (μg) taken 1 to 2 weeks before treatment and every 9 weeks until 3 weeks after last treatment dose. Folic Acid administered orally (po): 350 μg to 1000 μg taken 1 to 2 weeks before treatment and continue daily until 3 weeks after last treatment dose. |
| Pemetrexed | EXPERIMENTAL | - |
| Docetaxel | ACTIVE_COMPARATOR | - |
| A | EXPERIMENTAL | - |
| B | ACTIVE_COMPARATOR | - |
| Pemetrexed and Best Supportive Care | EXPERIMENTAL | - |
| Placebo and Best Supportive Care | PLACEBO_COMPARATOR | - |
| Cetuximab & Pemetrexed | EXPERIMENTAL | - |
| Cetuximab & Docetaxel | EXPERIMENTAL | - |
| bevacizumab+ pemetrexed | EXPERIMENTAL | pemetrexed (500 mg/m² IV) + bevacizumab (15 mg/kg IV). In addition to Vitamin B12 + Folate + Dexamethasone |
| Investigational Treatment | EXPERIMENTAL | * Pemetrexed 500 mg/m2 IV over 10 minutes, day 1 of 21-day cycle * Oral Folic Acid, once per day for 7 days preceding pemetrexed dose, continued daily, and for 21 days after the last dose of pemetrexed. * Vitamin B12, 1000ug intramuscular injection 7 days preceding pemetrexed dose, and every three cycles thereafter on the same day of pemetrexed administration |
| Intervention | EXPERIMENTAL | Chemotherapy-naïve patients with unresectable stage III/IV NSCLC received pemetrexed 500 mg/m2 IV and gemcitabine 1500 mg/m2 IV every 2 weeks for 8-12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy. |
| Pemetrexed/Carboplatin | EXPERIMENTAL | 4 cycles of preoperative treatment (1 Cycle = 21 days): Pemetrexed: 500 mg/m2 intravenously (IV) for 10 minutes on Day 1 each cycle; Carboplatin: AUC 6.0 by IV on Day 1 each cycle. |
| 250 mg Gefitinib/500 mg Pemetrexed | EXPERIMENTAL | 250 milligrams (mg) Gefitinib taken orally once daily (QD) and 500 milligrams per square meter (mg/m²) Pemetrexed taken intravenously (IV) once every 3 weeks concurrently with Gefitinib taken orally QD. |
| 250 mg Gefitinib | ACTIVE_COMPARATOR | 250 milligrams (mg) Gefitinib taken orally QD |
| Pemetrexed + Cisplatin + Cixutumumab | EXPERIMENTAL | Induction Treatment: Pemetrexed 500 mg/m\^2 plus cisplatin 75 mg/m\^2 plus cixutumumab 20 mg/kg given intravenously (IV) on Day 1 of a 21 day cycle for up to 4 cycles. Two additional cycles of cisplatin may be given (6 cycles total) for patients with significant tumor size reduction, after sponsor approval. Maintenance Therapy: Pemetrexed 500 mg/m\^2 plus cixutumumab 20 mg/kg given IV every 21 days until progression of disease, unacceptable toxicity, or another withdrawal criterion is met. |
| Triplet Combination Therapy | EXPERIMENTAL | Cycle 1: Week 1 - Cetuximab 400 milligrams/square meter (mg/m²) on Day 1; Pemetrexed 500 mg/m² on Day 1; Carboplatin area under curve (AUC) 5 on Day 1 or Cisplatin 75 mg/m² on Day 1 Week 2 - Cetuximab 250 mg/m² on Day 1 Week 3 - Cetuximab 250 mg/m² on Day 1 Cycle 2-6: Week 1 - Cetuximab 250 mg/m² on Day 1; Pemetrexed 500 mg/m² on Day 1; Carboplatin AUC 5 on Day 1 or Cisplatin 75 mg/m² on Day 1 Week 2 - Cetuximab 250 mg/m² on Day 1 Week 3 - Cetuximab 250 mg/m² on Day 1 Following Cycle 6, Cetuximab Monotherapy: 250 mg/m² intravenously weekly on Day 1 |
| Pemetrexed + Cisplatin + Cetuximab | EXPERIMENTAL | Participants will receive pemetrexed,cisplatin and cetuximab for up to 6 cycles (21 days per cycle) followed by optional maintenance of pemetrexed and cetuximab until disease progression. Optional maintenance therapy is permitted after at least 4 cycles of triplet combination therapy have been given. Cetuximab will be administered as an initial dose of 400 milligram per meter squared (mg/m\^2) intravenous (IV) infusion and as a 250 mg/m\^2 IV weekly dose thereafter. As Standard of care dietary supplements included: 350 to 1000 micrograms (µg) oral Folic Acid 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed and 1000 µg vitamin B12 intramuscular injection (IM) during the week preceding the first dose of pemetrexed and every 9 weeks thereafter. |
| Study Treatment | EXPERIMENTAL | - |
| Induction/maintenance Therapy | EXPERIMENTAL | pemetrexed, cisplatin and cetuximab followed by pemetrexed and cetuximab |
| Standard Vitamin and Steroid Schedule + Pemetrexed | ACTIVE_COMPARATOR | Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment. |
| Simplified Vitamin and Steroid Schedule + Pemetrexed | EXPERIMENTAL | Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only. |
| A: Pemetrexed + Best Supportive Care | EXPERIMENTAL | Pemetrexed: 500 milligrams per square meter (mg/m²) , intravenous (IV), Day 1 of each 21-day cycle for 6 cycles Best Supportive Care: Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician. |
| B: Best Supportive Care | ACTIVE_COMPARATOR | Best Supportive Care: Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician. |
| Pemetrexed + Erlotinib | EXPERIMENTAL | Pemetrexed 500 milligrams per meter squared (mg/m\^2) of body surface area, administered by intravenous (IV) infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months. |
| Erlotinib | ACTIVE_COMPARATOR | Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months. |
| Pemetrexed (Nonsquamous) | EXPERIMENTAL | Group of participants with non-small cell lung cancer (NSCLC) of nonsquamous histology who were assigned to Pemetrexed arm |
| Pemetrexed + Erlotinib (Nonsquamous) | EXPERIMENTAL | Group of participants with NSCLC of nonsquamous histology who were assigned to Pemetrexed + Erlotinib arm |
| Pemetrexed (Squamous) | EXPERIMENTAL | Group of participants with NSCLC of squamous histology who were assigned to Pemetrexed arm |
| Pemetrexed + Erlotinib (Squamous) | EXPERIMENTAL | Group of participants with NSCLC of squamous histology who were assigned to Pemetrexed + Erlotinib arm |
| Cohort A | EXPERIMENTAL | Cohort A, will receive bevacizumab 10mg/kg by vein over 30-90 minutes followed by pemetrexed 500 mg/m2 by vein over 10 minutes followed by gemcitabine 1500 mg/m2 by vein over 30-60 minutes. This regimen will be given on day 1 and day 15 of each treatment cycle. Each cycle is 28 days long. As long as their disease does not worsen patients can receive up to a maximum of 6 cycles of this combination chemotherapy. Following that they can receive bevacizumab alone once every 2 weeks as long as their disease does not worsen. |
| Cohort B | EXPERIMENTAL | Cohort B, will receive bevacizumab 15mg/kg by vein over 30-90 minutes followed by pemetrexed 500 mg/m2 by vein over approximately 10 minutes followed by carboplatin AUC=5 by vein over 30-60 minutes. This regimen will be given on day 1 of each treatment cycle. Each cycle is 21 days long. As long as their disease does not worsen patients can receive up to a maximum of 6 cycles of this combination chemotherapy. Following that they can receive bevacizumab alone once every 3 weeks as long as their disease does not worsen. |
| Pemetrexed/Cisplatin/Gefitinib | EXPERIMENTAL | Pemetrexed 500 milligrams per meters squared (mg/m2) plus cisplatin 75 mg/m2 administered by intravenous (IV) infusion once every 3 weeks for 4 cycles without progression followed by gefitinib 250 mg administered orally, once daily, until disease progression or unacceptable toxicity. |
| Pemetrexed + Carboplatin | EXPERIMENTAL | - |
| Gemcitabine/Vinorelbine | ACTIVE_COMPARATOR | Vinorelbine 30 mg/m\^2 was given over approximately 6-10 minutes on Day 1 and Day 8. Gemcitabine 1200 mg/m\^2 was given over approximately 30 minutes on Day 1 and Day 8 beginning after the end of the Vinorelbine infusion. The cycle of treatment was 21 days. |
| A: Pemetrexed + Cisplatin | EXPERIMENTAL | - |
| B: Pemetrexed + Carboplatin | EXPERIMENTAL | - |
| Pemetrexed & Bevacizumab | EXPERIMENTAL | - |
| A: Pemetrexed Plus Doxorubicin, Followed by Docetaxel | EXPERIMENTAL | - |
| B: Cyclophosphamide Plus Doxorubicin, Followed by Docetaxel | ACTIVE_COMPARATOR | - |
| Pemetrexed 500 mg/m2 | EXPERIMENTAL | Pemetrexed 500 mg/m2 |
| Pemetrexed 1000 mg/m2 | EXPERIMENTAL | Pemetrexed 1000 mg/m2 |
| Pemetrexed + Irinotecan | EXPERIMENTAL | - |
| Intrathecal Dual Checkpoint Inhibition in Combination with Pemetrexed | EXPERIMENTAL | This study is a prospective, single-arm, Phase I/II clinical trial. The primary objectives were to determine the recommended dose of intrathecal dual checkpoint inhibitor (PD-1 and CTLA-4, QL1706) in combination with pemetrexed and safety based on the incidence of treatment-related adverse events. Clinical response rate (CRR), disease control rate (DCR) and overall survival (OS) are also evaluated. Patients will have cerebrospinal fluid (CSF) and blood specimen collection for the evaluation of predictors (clinical, molecular, and/or immune) of the efficacy and safety of this regimen. |
| Phase 1: LY2603618 130 to 275 mg | EXPERIMENTAL | Cycle 1-2 (21-day cycle): Day 1: pemetrexed 500 milligrams per meter square (mg/m\^2) + cisplatin 75 mg/m\^2 Day 2: LY2603618 at 130-275 milligrams (mg) After 2 cycles, participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met. |
| Phase 2: Pemetrexed + Cisplatin + LY2603618 | EXPERIMENTAL | Cycles 1-4 (21-day cycle): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2 Day 2: LY2603618 dose from phase 1 portion of trial After 25 Oct 2012: Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2 After 4 cycles, participants may continue on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion is met. Maintenance Therapy Experimental Arm (every 21 days): Before 25 Oct 2012: Day 1: pemetrexed 500 mg/m\^2 Day 2: LY2603618 dose determined from phase 1 After 25 Oct 2012: Day 1: pemetrexed 500 mg/m\^2 If, as of 25 Oct 2012, participant was in maintenance therapy and randomized to the experimental arm, the participant is eligible to continue with pemetrexed (Day 1)/LY2603618 (Day 2) therapy if the investigator deems it is in the best interest of the participant and the participant consents. |
| Phase 2: Pemetrexed + Cisplatin | ACTIVE_COMPARATOR | Cycle 1-4 (21-day cycle): Day 1: pemetrexed 500 mg/m\^2 + cisplatin 75 mg/m\^2 After 4 cycles, participants may continue on maintenance therapy until disease progression, unacceptable toxicity, or other withdrawal criterion is met. Maintenance Therapy Comparator Arm: Phase 2 (every 21 days): Day 1: pemetrexed 500 mg/m\^2 |
| A: Pemetrexed + Carboplatin | EXPERIMENTAL | Pemetrexed + Carboplatin |
| B: Pemetrexed + Cisplatin | EXPERIMENTAL | Pemetrexed + Cisplatin |
| Pemetrexed/Cisplatin/Radiation Phase 1 | EXPERIMENTAL | Treatment included: radiation as 61-65 Gray (Gy) in 33-35 fractions if 2-phase treatment and 62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent pemetrexed intravenous (IV) bolus with doses escalating from 300 milligrams per square meter (mg/m\^2) IV through 500 mg/m\^2 IV on Days 1 and 22; concurrent cisplatin 25 mg/m\^2 IV on Days 1-3 and 22-24 for Cohorts 1-3 and cisplatin 20 mg/m\^2 IV on Days 1-5 and 22-26 for Cohort 4. Participants then received 2 additional consolidation cycles repeated every 3 weeks (q3 weeks) of pemetrexed 500 mg/m\^2 IV and cisplatin 75 mg/m\^2 IV. |
| Pemetrexed/Cisplatin/Radiation Phase 2 | EXPERIMENTAL | Treatment included: radiation, 61-65 Gy in 33-35 fractions if 2-phase treatment and 62-66 Gy in 31-33 fractions if 1-phase treatment; concurrent phase pemetrexed IV bolus as determined by Phase 1 trial to be 500 mg/m\^2 IV on Days 1 and 22 ; concurrent cisplatin 20 mg/m\^2 IV as determined by Phase 1 trial with cycles commencing on Days 1 and 22; 2 additional consolidation cycles (q3 weeks) of pemetrexed 500 mg/m\^2 IV and cisplatin 75 mg/m\^2 IV. |
| Pemetrexed/Carboplatin Phase 1 | EXPERIMENTAL | Pemetrexed was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Pemetrexed/Carboplatin Phase 2 | EXPERIMENTAL | Pemetrexed was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. |
| Pemetrexed 600 mg/m2 | EXPERIMENTAL | - |
| Pemetrexed 1800 mg/m2 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Pemetrexed | DRUG | 500 milligram per square meter (mg/m2) administered Intravenously (I.V.) on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Cisplatin | DRUG | 75 mg/m2 administered I.V. on Day 1 of every 3-week cycle, for a maximum of six cycles |
| Necitumumab | BIOLOGICAL | 800 mg (absolute dose) on Days 1 and 8 of every 3-week cycle, administered as an I.V. |
| Gemcitabine | DRUG | 1250 mg/m² administered intravenously on Day 1 and Day 8 of each 21-day cycle, for 6 cycles |
| Gefitinib | DRUG | 250 milligrams (mg) administered orally once a day, every day of 21-day cycle, for maintenance in participants with non-progressive disease after cisplatin/pemetrexed chemotherapy |
| Carboplatin | DRUG | Induction Therapy (every 21 days for 4 cycles): Area Under the Curve (AUC) 6 \[maximum possible dose of 900 milligrams (mg)\] intravenously infused over 30 minutes. |
| Paclitaxel | DRUG | Induction Therapy (every 21 days for 4 cycles): 200 mg/m² intravenously infused over 3 hours |
| Bevacizumab | BIOLOGICAL | Induction therapy: 15 milligrams/kilogram (mg/kg) given intravenously every 21 days for 4 cycles. Maintenance therapy: 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation. |
| Placebo | DRUG | Maintenance therapy: Normal saline (0.9% sodium chloride) administered IV on Day 1 every 21-day cycle until progressive disease or treatment discontinuation |
| Best Supportive Care | OTHER | Best Supportive Care is treatment given with the intent to maximize quality of life. Best Supportive Care excludes any treatment in which the goal is to cure or slow the progression of the study disease. Patients will receive Best Supportive Care as judged by their treating physician. Those therapies considered acceptable include, but are not limited to, palliative radiation to extrathoracic structures, antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, and/or nutritional support (enteral or parenteral). |
| Etoposide | DRUG | administered per local practice guidelines over a minimum of 30 minutes |
| Vinorelbine | DRUG | administered over 6-10 minutes infusion per local practice guidelines |
| Thoracic Radiation Therapy (TRT) | RADIATION | - |
| docetaxel | DRUG | 75 mg/m\^2, IV, q 21 days x 6 cycles maximum |
| Cetuximab | BIOLOGICAL | Cetuximab 400/250 mg/m\^2 (initial/weekly) administered intravenously on Days 1, 8, and 15 (3-week) cycles until disease progression or unacceptable toxicity. |
| Vitamin B12 | DRUG | 1000 micrograms, IM injection 1-2 weeks prior to treatment and repeated every 9 weeks until last dose of pemetrexed |
| Folate | DRUG | 350 to 1000 micrograms 1 week prior to treatment and 3 weeks after last pemetrexed dose |
| Dexamethasone | DRUG | 4 mg; oral, twice a day at the following times: the day before, of and after each dose of pemetrexed |
| Folic Acid | DIETARY_SUPPLEMENT | All participants received oral Folic Acid 350-100ug once per day for 7 days preceding the first pemetrexed dose and continuing throughout the study and and for 21 days after the last dose of pemetrexed. |
| Cixutumumab | DRUG | Administered IV |
| Thoracic Radiotherapy | RADIATION | Administered at 2 gray (Gy)/fraction after completion of the pemetrexed and cisplatin infusions on Day 1 of Cycle 3 and will continue daily (5 days per week) until the total delivered dose reaches a therapeutic goal of 66 Gy, over approximately 7 weeks. |
| erlotinib | DRUG | 150 mg, orally, once daily until progression or unacceptable toxicity develops |
| Pemetrexed and Gemcitabine plus Bevacizumab | DRUG | Bevacizumab 10 mg/kg will be given intravenously according to weight. Pemetrexed 500 mg/m\^2 and gemcitabine 1500 mg/m\^2 will be given intravenously according to weight and height. All agents are administered every 2 weeks. |
| cyclophosphamide | DRUG | 600 mg/m2, intravenous (IV), every 21 days, 4 cycles (1-4) |
| doxorubicin | DRUG | 60 mg/m\^2, intravenous (IV), every 21 days, 4 cycles (1-4) |
| Radical Non-Small Cell Lung Cancer (NSCLC) surgery | PROCEDURE | All participants proceeded to surgery within 4-8 weeks from the last dose of pemetrexed. |
| Pemetrexed 500 mg/m2 | DRUG | 500 mg/m2, intravenous (IV), every 21 days, one year from registration date |
| Pemetrexed 1000 mg/m2 | DRUG | 1000 mg/m2, intravenous (IV), every 21 days, one year from registration date |
| irinotecan | DRUG | 180 mg/m\^2, intravenous (IV), every 14 days x 12 cycles |
| oxaliplatin | DRUG | - |
| ALIMTA | DRUG | - |
| Pemetrexed (Alimta) in combination with gemcitabine (Gemzar) | DRUG | - |
| QL1706 (bispecific antibody targeting PD-1 and CLTA-4) | DRUG | Intrathecal injection of PD-1/CTLA-4 bispecific antibody was administered every 2 weeks for 6 weeks during the induction phase, followed by monthly injections during the maintenance phase, until recurrence or death. |
| Pemetrexed (Alimta) | DRUG | Pemetrexed (Alimta, Eli Lilly and Company) was administrated by intrathecal injection, first as induction therapy, twice per week for 2 weeks, followed by consolidation therapy, once per week for 4 weeks, then maintenance therapy, once per month until the patient's death, leptomeningeal metastasis progresses, or intolerable severe adverse events occurred. |
| LY2603618 | DRUG | Administered intravenously as a continuous 1-hour infusion |
| radiation therapy | RADIATION | Phase 1 - 2 Gray, daily, 5 days a week for Days 1-51 Phase 2 - 2 Gray, daily, 5 days a week for Days 1-45 |
| Pemetrexed Phase 1 | DRUG | 300 mg/m\^2 IV, Days 1 and 22; intermediate dose escalation level of 400 mg/m\^2 IV; then 500 mg/m\^2 IV, repeated every 21 days (q 21 days) x 2 cycles |
| Cisplatin Phase 1 | DRUG | Cohorts 1-3: 25 mg/m\^2 IV, Days 1-3 and 22-24 then 75 mg/m\^2 IV, q21 days x 2 cycles Cohort 4 carried into Phase 2: 20 mg/m\^2 IV, Days 1-5 and 22-26 then 75 mg/m\^2 IV, q21 days x 2 cycles. |
| Pemetrexed Phase 2 | DRUG | Concurrent phase pemetrexed IV bolus as determined by Phase 1 trial to be 500 mg/m\^2 IV on Days 1 and 22. |
| Cisplatin Phase 2 | DRUG | Phase 2 (Cohort 4 carried over from Phase 1): 20 mg/m\^2 IV, Days 1-5 and 22-26 then 75 mg/m\^2 IV, q21 days x 2 cycles. |
| Pemetrexed - Phase 1 | DRUG | 500, 600, 700, 800, or 900 milligrams per square meter (mg/m\^2), administered intravenously (IV), every 21 days x 6 cycles, dose escalate to Maximum Tolerated Dose (MTD) |
| Carboplatin - Phase 1 | DRUG | area under the concentration time curve (AUC) 5 or 6 mg/mL\*min, administered intravenously (IV), every 21 days x 6 cycles, dose escalation to Maximum Tolerated Dose (MTD) |
| Pemetrexed - Phase 2 | DRUG | Dose determined from Phase 1: 500 mg/m\^2, administered IV, every 21 days x 6 cycles |
| Carboplatin - Phase 2 | DRUG | Dose determined from Phase 1: AUC 6 mg/mL\*min, administered IV, every 21 days x 6 cycles |
| Platinol | DRUG | - |
| multi-vitamins | DRUG | - |
| ALIMTA plus Epirubicin | DRUG | - |
Inclusion Criteria: * Has histologically or cytologically confirmed nonsquamous (adenocarcinoma/large cell or other) non small cell lung cancer * Has Stage IV disease at the time of study entry * Measurable or nonmeasurable disease (as defined by the Response Evaluation Criteria in Solid Tumors REC...
ALIMTA is a small molecule oncology drug developed by Eli Lilly and Company. It has been studied in clinical trials for several cancer types, including breast cancer, non-small cell lung cancer, small cell lung cancer, colorectal cancer, and urologic neoplasms. It is also studied in combination regimens such as ALIMTA plus epirubicin.
ALIMTA has been studied in combination with epirubicin for patients with locally advanced or metastatic breast cancer. That Phase 1 trial, NCT00097383, enrolled adult women and was completed. ALIMTA is also studied across other tumor types, including non-small cell lung cancer and colorectal cancer.
ALIMTA is developed by Eli Lilly and Company, which trades under the ticker LLY. The company has sponsored clinical trials of ALIMTA both as a single agent and in combination with other chemotherapy agents such as epirubicin, cisplatin, carboplatin, and oxaliplatin.
ALIMTA is an investigational agent that has been studied in Phase 1 and Phase 2 clinical trials. The Phase 1 study evaluated ALIMTA plus epirubicin in breast cancer, while Phase 2 studies evaluated ALIMTA combinations in small cell lung cancer, non-small cell lung cancer, and colorectal cancer.
ALIMTA has been studied in completed trials including NCT00097383 in breast cancer, NCT00051506 in extensive stage small cell lung cancer, NCT00051493 in non-small cell lung cancer, and NCT00034619 in advanced colorectal cancer. These studies evaluated ALIMTA alone and in combination with other chemotherapy agents.