Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
IMC-A12 · 9 trials · 12 indications
ORR was defined as the percentage of participants achieving either CR or PR. Response was defined using Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions and the normalization of the tumour marker level. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Percentage of participants is calculated as a total number of participants with CR or PR / total number of participants treated \* 100.
Defined as the median time from randomization to the earliest of: 1. Tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST); 2. Evidence of progression by bone scan, performed after completion of the first 3 cycles, demonstrating the appearance of \>=2 new lesions; 3. New skeletal events (New pathologic bone fracture in the region of metastatic disease; New bone lesion requiring radiation or surgery; Spinal cord or nerve root compression) 4. Symptomatic progression (for participants without measurable disease); 5. Other clinical events attributable to prostate cancer that require major interventions; or 6. Death from any cause Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.
PFS is defined as the time from the date of randomization until date of objectively determined progressive disease (PD) or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a ≥20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions unequivocal progression of non-target lesions. Participants without documentation of progression or death will be censored at the date of last tumor assessment. The PFS will be estimated following the Kaplan-Meier method.
OS is defined as the interval between date of randomization and the date of death due to any cause. Participants who are alive at the time of study completion will be censored at the time the participants was last known to be alive.
PFS at 12 weeks was reported by disease condition and defined as the percentage of participants who have neither experienced disease progression nor died at 12 weeks after the date of first dose. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive Disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. Percentage of participants is calculated as the total number of participants with PFS at 12 weeks divided by the total number of participants treated then multiplied by 100.
cTTP was the time from the first day of treatment to the earliest onset of 1 of the following: tumor progression by Response Evaluation Criteria In Solid Tumors \[RECIST, version 1.0\] criteria: unequivocal evidence of progression by bone scan, new skeletal events, symptomatic progression (for participants without measurable disease), or other clinical events attributable to prostate cancer that in the opinion of the investigator require major interventions. Participants without tumor progression at data cut-off were censored.
ORR is the percentage of participants with a confirmed CR or PR, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. ORR is calculated as a total number of participants with CR or PR from start of the treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.
Data presented are the number of participants who experienced serious adverse events (SAEs), other non-serious AEs and deaths during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT). A DLT was defined as any Grade 3 or 4 hematologic or nonhematologic toxicity based on Common Terminology Criteria for AE (CTCAE), excluding alopecia, which was considered by the investigator to be definitely, probably, or possibly related to IMC-A12.
| Arm | Type | Description |
|---|---|---|
| GCiC + IMC-A12 (Gemcitabine/Cisplatin/Cetuximab + Cixutumumab) | EXPERIMENTAL | Cycles repeat every 3 weeks for first 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met \*Cisplatin will replace Carboplatin. Gemcitabine/Carboplatin/Cetuximab (GCC) plus cixutumumab will change to Gemcitabine/Cisplatin/Cetuximab (GCiC) plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab) |
| GCiC (Gemcitabine/Cisplatin/Cetuximab) | ACTIVE_COMPARATOR | Cycles repeat every 3 weeks for 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met \*Cisplatin will replace Carboplatin. GCC plus cixutumumab will change to GCiC plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab) |
| IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone | EXPERIMENTAL | - |
| IMC-A12 + Mitoxantrone + Prednisone | EXPERIMENTAL | - |
| IMC-A12 (cixutumumab) + antiestrogen therapy | ACTIVE_COMPARATOR | Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory. |
| IMC-A12 (cixutumumab) | EXPERIMENTAL | Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks). |
| IMC-A12 (cixutumumab) + cetuximab | EXPERIMENTAL | - |
| IMC-A12 | EXPERIMENTAL | Thirty-one participants will receive IMC-A12 at 10 milligrams per kilogram (mg/kg) administered over 1 hour every other week (every 14 days). An additional 10 participants will receive IMC-A12 at a dose of 20 mg/kg every three weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Radiographic evaluation of response will be performed every 8 weeks for the participants treated with intravenous (i.v.) IMC-A12 at 10 mg/kg and every 9 weeks for the participants treated with i.v. IMC-A12 at 20 mg/kg. |
| IMC-A12 + cetuximab | EXPERIMENTAL | Administered every 2 weeks |
| IMC-A12 + cetuximab [Kirsten rat sarcoma (K-ras) wild-type] | EXPERIMENTAL | Participants who have experienced confirmed partial response (PR) or stable disease (SD) ≥ 24 weeks on a prior anti-EGFR-containing therapy followed by disease progression are enrolled in this arm. |
| Name | Type | Description |
|---|---|---|
| Gemcitabine | DRUG | 1000 milligrams per square meter (mg/m\^2) on Days 1 and 8 of each cycle \[First 6 cycles (18 weeks)\] |
| Cisplatin | DRUG | 75 mg/m\^2 on Day 1 of each cycle \[First 6 cycles (18 weeks)\] |
| IMC-A12 (cixutumumab) | BIOLOGICAL | 6 milligrams per kilogram (mg/kg) intravenous (IV) infusion, administered once per week (on Days 1, 8, and 15 of each cycle) \[First 6 cycles (18 weeks)\] |
| Cetuximab | BIOLOGICAL | 400 mg/m\^2 IV infusion, administered on Day 1 of Cycle 1, 250 mg/m\^2 once per week thereafter \[First 6 cycles (18 weeks)\] |
| Carboplatin | DRUG | Area under the curve (AUC) = 5, Day 1 of each cycle \[First 6 cycles (18 weeks)\] \*Carboplatin will be replaced by Cisplatin |
| IMC-A12 | BIOLOGICAL | IMC-A12 is to be administered as an I.V. infusion, 6 mg/kg over 1 hour on Days 1, 8, and 15 of each 3-week (21-day) cycle. IMC-A12 treatment is to continue until there is evidence of disease progression, death, intolerable toxicity, or other withdrawal criteria are met. |
| Mitoxantrone | DRUG | Mitoxantrone is to be administered as an I.V. infusion, at 12 milligrams/square meter (mg/m\^2) over 5-15 minutes on Day 1 during a 3-week (21-day) cycle. Mitoxantrone treatment is to be continued for a maximum of 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤ 144 mg/m\^2) or until there is evidence of disease progression, death, or intolerable toxicity. |
| Prednisone | DRUG | Prednisone (5 mg) is to be self-administered PO BID, each day of the 21-day cycle. |
| IMC-1121B (ramucirumab) | BIOLOGICAL | IMC-1121B (ramucirumab) is to be administered as an intravenous (IV) infusion, 6 milligrams/kilogram (mg/kg) over 1 hour on Days 1, 8, and 15 of each 3-week (21-day) cycle. Ramucirumab treatment is to continue until there is evidence of disease progression, death, intolerable toxicity, or other withdrawal criteria are met. |
| tamoxifen | DRUG | Daily 20 mg, oral |
| Anastrozole | DRUG | Daily 1 mg, oral |
| Letrozole | DRUG | Daily 2.5 mg, oral |
| Exemestane | DRUG | Daily 25 mg, oral |
| Fulvestrant | DRUG | Monthly 250 mg, intramuscularly |
| cetuximab (Erbitux ®) | BIOLOGICAL | IMC-A12 10 mg/kg over one hour followed by cetuximab 500 milligrams per square meter (mg/m\^2) over two hours. This sequence will be repeated every two weeks. Participants will continue on study until evidence of progressive disease or unacceptable toxicity develops. |
Inclusion Criteria: * Has histologically or cytologically confirmed, Stage IIIb - IV NSCLC * Has metastatic disease * Has a tumor measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) * Has adequate hematologic function * Has adequate hepatic function * Has adequate renal fu...
IMC-A12 is an investigational oncology drug being studied for advanced solid tumors, Ewing's Sarcoma/Peripheral Neuroectodermal Tumor (PNET), head and neck cancer, non-small cell lung cancer, colorectal cancer, and adenocarcinoma of the prostate. It is a small molecule in Phase 2 clinical development.
IMC-A12 is being developed by Eli Lilly and Company (NYSE: LLY). The drug is an investigational small molecule in Phase 2 clinical development for multiple oncology indications, including advanced solid tumors and Ewing's Sarcoma/Peripheral Neuroectodermal Tumor (PNET).
IMC-A12 is in Phase 2 clinical development. It is an investigational drug and has not been approved by the FDA. Clinical trials have been completed for indications including adenocarcinoma of the prostate and advanced sarcoma, but the drug remains investigational.
IMC-A12 has completed several clinical trials. NCT00520481 studied it in metastatic prostate cancer with 41 participants. NCT00668148 studied it in advanced sarcoma with 113 participants. NCT00785538 and NCT00785941 studied it in advanced solid tumors with 24 and 16 participants respectively.
Yes, IMC-A12 is also known as cixutumumab. Clinical trial NCT00520481, titled 'Study With IMC-A12 (Cixutumumab) in Patients Who Have Not Previously Been Treated With Chemotherapy With Metastatic Prostate Cancer,' confirms that IMC-A12 and cixutumumab refer to the same drug.