Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication XALKORI is a kinase inhibitor indicated for the treatment of • adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test. ( 1.1 , 2.1 ) • pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. FDA label
Also known as cMET inhibitor, Crizotinib, Xalkori
PF-02341066 · 10 trials · 14 indications
PFS was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression (by IRR) or death on study due to any cause, whichever occured first. If tumor progression data included more than 1 date, the first date was used. PFS (in months) was calculated as (first event date - randomization date +1)/30.44. Progression is defined using RECIST v1.1, as at least a 20% increase (including an absolute increase of at least 5 millimeters) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
PFS: Time in months from randomization to first documentation of objective disease progression as determined by independent radiology review or to death due to any cause, whichever occurred first. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria version 1.1 (RECIST v1.1), as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Overall objective response (ORR) was defined as the number of patients with a best overall response of confirmed Complete Response or confirmed Partial Response according to RECIST v1.1 (as determined by Independent Radiology Review \[IRR\]), relative to the total population of response-evaluable participants. Per RECIST v1.1, CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis); PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. Confirmed responses were those that persisted on repeat imaging at least 4 weeks after the initial documentation of response.
The objective response rate (ORR) as a measure of anti-tumor efficacy of oral PF-02341066 in participants with advanced NSCLC with an ALK gene translocation or inversion after failure of at least one line of chemotherapy.
Incidence of adverse events and laboratory abnormalities (severity graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\], version 4.0).
Rate of dose limiting toxicity (DLT) in the first 28 days of study therapy by dose level when escalating doses of crizotinib are combined with enzalutamide and when appropriate a GnRH agonist.
Area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1.
AE was any untoward medical occurrence with study drug/ device in a trial participant. Serious adverse event (SAE) was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.
AE was any untoward medical occurrence with study drug/ device in a trial participant. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.
An AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.
An AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.
DLTs were those AEs which occurred in Cycle 1 of treatment in Dose Escalation Phase which may be attributed to study drug \[combined Crizotinib (PF-02341066) plus Dacomitinib (PF-00299804)\] without a clear alternative explanation and despite the use of adequate/maximal medical intervention as dictated by local institutional clinical practices or the judgment of the investigator. The following events were considered DLTs (using CTCAE version 4.02);1. Grade ≥4 hematologic events. 2. Grade ≥3 non-hematological events (except Grade 3/4 asymptomatic hypophosphatemia and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting or diarrhea had to have persisted at Grade 3 or 4 despite maximal medical therapy. Grade 3 hypertension will be considered a DLT only if the event is unmanageable by standard approved pharmacologic agents or if the symptomatic sequelae are identified despite appropriate medical intervention.
Phase 1, first cycle DLT includes Grade (Gr) ≥4 hematologic possible drug-related toxicities and Gr ≥3 possible drug-related febrile neutropenia. Gr ≥3 non-hematological possible drug-related toxicities (except asymptomatic lab value elevation). Gr 3/4 nausea, vomiting or diarrhea. Gr 3 hypertension considered DLT if event unmanageable by approved pharmacologic agents or symptomatic sequelae despite medical intervention. Diagnosis of interstitial lung disease. Inability to deliver at least 80 percent (%) of planned dose during cycle 1 due to possible drug-related adverse events (AEs).
Time in weeks from phase 2 study randomization to first documentation of objective disease progression or death due to any cause. Progression-Free Survival was calculated as (first event date minus randomization date plus 1) divided by 7.02. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from AE data (where the outcome was "Death"; date of death reported in notice of death was used).
MTD: Dose level at which at most 1 of 6 participants experienced DLT within and including 28 days of treatment (during Cycle 1 \[1 cycle=28 days\]) with next higher dose having at least 2/3 or 2/6 participants experiencing a DLT. DLT was defined as any of following: Hematologic toxicities- 1) prolonged grade 4 neutropenia for \>7 days. 2) Febrile neutropenia: grade 4 neutropenia with fever greater than (\>) 38.5 degree Celsius, both sustained over a 24 hour period (3) neutropenic infection: greater than or equal to (\>=) Grade 3 neutropenia with Grade \>=3 infection. (4) Grade \>=3 thrombocytopenia with bleeding/grade 4 lasting \>=7 days. Other non-hematologic toxicity included: Grade 3/4 toxicities (except for alopecia, Grade 3/4 hypophosphatemia, grade 3 hypertension with controlled blood pressure \[less than (\<) 140/90 millimeter of mercury, and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting/diarrhea must persist at grade 3/4 despite maximal medical therapy.
RP2D was defined as a dose below or equal to MTD, at which crizotinib was unlikely to cause a significant inhibition of CYP3A4 activity.
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (0-inf).
Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.
Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.
Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.
Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.
Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.
Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.
Cmax is defined as the observed maximum plasma concentration post drug administration.
Cmax is defined as the observed maximum plasma concentration post drug administration.
Cmax is defined as the observed maximum plasma concentration post drug administration.
Cmax is defined as the observed maximum plasma concentration post drug administration.
Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).
Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).
Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).
Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).
Plasma decay half-life is the time measured for the plasma concentration of Crizotinib to decrease by one half.
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. AEs included both serious and all non-serious adverse events. TEAEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration.
Dose-limiting toxicity (DLT) was defined as any of the following: Hematologic- prolonged grade 4 neutropenia for \>7 days. Febrile neutropenia, defined as grade 4 neutropenia with fever greater than (\>)38.5 degree Celsius, both sustained over a 24 hour period, neutropenic infection: greater than or equal to (\>=)Grade 3 neutropenia with Grade \>=3 infection. Grade \>=3 thrombocytopenia with bleeding or grade 4 lasting \>=7 days Lymphopenia was not considered a DLT unless accompanied by infection. Other non-hematologic toxicity: Grade 3 or 4 toxicities (except for alopecia, Grade 3/4 hypophosphatemia, grade 3 hypertension with controlled blood pressure \[less than (\<) 140/90\], and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting or diarrhea must persist at grade 3 or 4 despite maximal medical therapy.
Cmax is defined as the observed maximum plasma concentration post drug administration.
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
AUC0-24 of Crizotinib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
Cmax is defined as the observed maximum plasma concentration post drug administration.
Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau).
Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.
Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours.
Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.
ORR was defined as participants with a best overall response of complete response (CR) or partial response (PR) divided by the total number of evaluable participants per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response.
Duration of response (DoR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. PD: \>=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.
TTR: time between first dose until first documented response of PR or CR. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response.
Disease control was defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Disease control was defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Progression free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PD: \>=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.
Probability of being event free (event defined as PD or death due to any cause) at 6 months after the first dose of crizotinib was reported. PD: \>=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.
OS was defined as the time from randomization to death due to any cause.
Probability of survival was defined as the probability of being alive at Month 6.
Probability of survival was defined as the probability of being alive at Month 12.
Geometric mean of ratio (Cycle1Day15/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.
Geometric mean of ratio (Cycle 2 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.
Geometric mean of ratio (Cycle 4 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.
Geometric mean of ratio (Cycle 6 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.
Geometric mean of ratio (Cycle 9 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.
Geometric mean of ratio (Cycle 12 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.
Geometric mean of ratio (Cycle 15 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.
Geometric mean of ratio (Cycle 18 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.
Geometric mean of ratio (Cycle 21 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.
Geometric mean of ratio (Cycle 24 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.
Geometric mean of ratio (Cycle 27 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.
Geometric mean of ratio (Cycle 30 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.
Geometric mean of ratio (End of treatment/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.
| Arm | Type | Description |
|---|---|---|
| Crizotinib | EXPERIMENTAL | Crizotinib |
| Chemotherapy | ACTIVE_COMPARATOR | Chemotherapy \[Option at Investigator's Choice\] |
| PF-02341066 | EXPERIMENTAL | - |
| Pemetrexed or Docetaxel | ACTIVE_COMPARATOR | Investigator selection of either pemetrexed or docetaxel as the active comparator |
| PF-0231066 | EXPERIMENTAL | - |
| crizotinib and enzalutamide | EXPERIMENTAL | A traditional 3+3 dose escalation scheme will be used to identify the recommended phase 2 dose (RP2D) of crizotinib when used in combination with standard fixed dose enzalutamide. * Crizotinib- given orally daily-28 day cycle * Enzalutamide- given orally daily-28 day cycle |
| A1: normal hepatic function | EXPERIMENTAL | - |
| A2: normal hepatic function | EXPERIMENTAL | - |
| B: mild hepatic impairment | EXPERIMENTAL | - |
| C: moderate hepatic impairment | EXPERIMENTAL | - |
| D: severe hepatic impairment | EXPERIMENTAL | - |
| Arm A | OTHER | CLCR: Creatinine clearance |
| Arm B | OTHER | CLCR: Creatinine clearance |
| Arm 1 | EXPERIMENTAL | PF-02341066 AND PF-00299804: Patients will be treated with combined cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804). |
| Arm 2 | EXPERIMENTAL | PF-00299804 FOLLOWED BY COMBINED PF-02341066 AND PF-00299804: Patients will be treated with single agent panHER inhibitor (PF-00299804) until disease progression and then with the maximum tolerated combined dose of cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804). |
| Erlotinib | ACTIVE_COMPARATOR | - |
| Erlotinib + PF-02341066 | EXPERIMENTAL | - |
| 1 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Crizotinib | DRUG | 250 mg two times daily \[BID\], oral, on a continuous daily dosing schedule. Cycles are defined in 21 day periods. |
| Pemetrexed/Cisplatin | DRUG | Option 1: Pemetrexed/Cisplatin; Pemetrexed, 500 mg/m\^2, will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on Day 1 of a 21-day cycle. Cisplatin, 75 mg/m\^2 will be administered by infusion after adequate hydration according to institutional practices beginning approximately 30 minutes after the end of the pemetrexed infusion. Pemetrexed and cisplatin will be repeated every 3 weeks for a maximum of 6 cycles. |
| Pemetrexed/Carboplatin | DRUG | Option 2: Pemetrexed/Carboplatin. Pemetrexed, 500 mg/m\^2, will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on Day 1 of a 21-day cycle. Carboplatin, at a dose calculated to produce an AUC of 5 or 6 mg.min/mL will be administered by infusion according to institutional practices beginning approximately 30 minutes after the end of the pemetrexed infusion. Pemetrexed and carboplatin will be repeated every 3 weeks for a maximum of 6 cycles. |
| PF-02341066 | DRUG | PF-02341066, 250 mg BID will be administered orally on a continuous schedule |
| Pemetrexed | DRUG | Pemetrexed, 500 mg/m\^2, will be administered by i.v. infusion over 10 minutes on Day 1 of each 21-day cycle |
| Docetaxel | DRUG | Docetaxel, 75 mg/m\^2, will be administered by i.v. infusion over 1 hour on Day 1 of each 21-day cycle |
| Enzalutamide | DRUG | Enzalutamide is an androgen receptor signaling inhibitor. |
| PF-00299804 | DRUG | Arm 1: The starting dose will be 30 mg by mouth once a day of PF-0029804 in tablet form. The dose of each drug in the combination \[PF-02341066 and PF-00299804\] will be escalated or de-escalated until the maximum tolerated combined dose is reached. Patients will then be treated with the maximum tolerated combined dose. |
| Erlotinib | DRUG | Erlotinib, 150 mg, QD will be administered orally on a continuous schedule (Phase 2 only) |
| Rifampin | DRUG | 600 mg QD administered from Cycle 1, Day 16 to Cycle 2, Day 1 (14 days of dosing) in combination with PF-02341066. |
| Itraconazole | DRUG | Multiple Dose Design: 200 mg QD administered from Cycle 1, Day 1 to Cycle 1, Day 16 (16 days) in combination with PF-02341066. |
Inclusion Criteria: * Histologically or cytologically proven diagnosis of locally advanced not suitable for local treatment, recurrent and metastatic non-squamous cell carcinoma of the lung. * Positive for translocation or inversion events involving the ALK gene locus. * No prior systemic treatment...
PF-02341066 is an investigational small molecule being studied for non-small cell lung cancer, including ALK-positive non-small cell lung cancer. It has been evaluated in patients with advanced disease and a specific gene profile involving the anaplastic lymphoma kinase (ALK) gene, as well as in combination studies in non-small cell lung cancer.
PF-02341066 is being developed by Pfizer, Inc., which trades under the ticker PFE. Pfizer is the sponsor of the clinical trials evaluating the drug in non-small cell lung cancer, including the Phase 3 study comparing it with standard of care in patients whose tumors have an ALK gene profile.
PF-02341066 has reached Phase 3 development. The Phase 3 trial in advanced non-small cell lung cancer with an ALK gene profile has been completed, and earlier Phase 1 and Phase 2 studies in non-small cell lung cancer have also been completed. The drug remains investigational and is not described as approved.
PF-02341066 has been studied in completed trials including NCT00932893, a Phase 3 study versus standard of care in advanced ALK-positive non-small cell lung cancer, and NCT00932451, a Phase 2 study in the same gene-defined population. Phase 1 trials NCT01121575 and NCT00965731 evaluated combinations in non-small cell lung cancer.
PF-02341066 is a small molecule studied in tumors with a specific gene profile involving the anaplastic lymphoma kinase (ALK) gene. Its clinical program selected patients based on that ALK biomarker, and one Phase 1 trial combined it with a pan-HER inhibitor in non-small cell lung cancer.
Across the reported trials, 1,416 patients have been enrolled in studies of PF-02341066. The largest was the Phase 2 trial NCT00932451 with 1,069 patients, followed by the Phase 3 trial NCT00932893 with 347 patients. The Phase 3 study was randomized and actively controlled.