Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as IMC-A12 (cixutumumab), IMC-A12-kg, cixutumumab, LY3012217
IMC-A12 · 10 trials · 14 indications
Percentage of participants who are alive and progression-free at 6 month from start of the study treatment over all participants. PFS is defined as the time from the start of study treatment until the date of objectively determined progressive disease (PD) or death due to any cause. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, 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 of progression or death will be censored at the date of last tumor assessment. The PFS was estimated by the binomial distribution and Kaplan-Meier method.
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.
A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.
DLTs were defined as any cixutumumab-related Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0) Grade 3 or 4 adverse events (reported in the subsequent Primary Outcome Measure).
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 |
|---|---|---|
| Carcinoid tumor | EXPERIMENTAL | Participants with carcinoid tumor will receive cixutumumab 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen. |
| Islet cell carcinoma | EXPERIMENTAL | Participants with islet cell carcinoma will receive cixutumumab 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen. |
| 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. |
| Cixutumumab | EXPERIMENTAL | Participants receive IV cixutumumab every 2 or 3 weeks. A cycle equals 6 weeks, with radiological evaluation of tumor response after each cycle. After 1st cycle, pts with a complete response (CR), PR, or SD continue to receive cixutumumab cohort dose and schedule disease progression. 3 pts enroll in each cohort. Starting dose in Cohort 1 is 6 mg/kg every 2 weeks. Dose escalation from Cohort 1 to Cohort 2 (10 mg/kg every 2 weeks) occurs at least 3 pts in Cohort 1 completes 1 cycle of therapy. Enrollment into Cohort 3 (starting dose: 15 mg/kg administered every 3 weeks) will not proceed until at least 3 pts have completed one cycle of therapy in Cohort 2. Pts enroll in Cohort 4 once at least 3 pts have completed once cycle of therapy in Cohort 3; pts in Cohort 4 receive 20 mg/kg every 3 weeks. |
| Name | Type | Description |
|---|---|---|
| Cixutumumab | BIOLOGICAL | Participants will receive cixutumumab IV 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. |
| depot octreotide | DRUG | Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen. |
| 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. |
| IMC-A12 (cixutumumab) | BIOLOGICAL | 10 mg/kg I.V. |
| 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. |
| cetuximab | BIOLOGICAL | Participants will receive cetuximab 500 milligrams/square meter (mg/m²) intravenous over 2 hours every 2 weeks. |
Inclusion Criteria: * The participant has well-differentiated or moderately-differentiated, histologically confirmed neuroendocrine carcinoma, including carcinoid of any location and islet cell tumors * The participant has metastatic disease at the time of study entry * The participant must have a ...
IMC-A12 is an investigational monoclonal antibody being studied in oncology for several cancer types, including metastatic breast cancer, prostate cancer, advanced solid tumors, colorectal cancer, Ewing's sarcoma/peripheral neuroectodermal tumor (PNET), and head and neck cancer. It has been evaluated in Phase 1 and Phase 2 clinical trials.
IMC-A12 is being developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. The drug is an investigational monoclonal antibody in the oncology therapeutic area.
IMC-A12 is in Phase 2 clinical development. It has been studied in completed Phase 1 and Phase 2 trials, including a Phase 2 trial in metastatic breast cancer and a Phase 2 trial in prostate cancer. It is not approved by the FDA.
IMC-A12 has been evaluated in completed clinical trials including NCT00785941 and NCT00785538 in advanced solid tumors, NCT00728949 in metastatic breast cancer, and NCT00683475 in prostate cancer. All four trials are completed, and no trials are currently active.
Yes, IMC-A12 is also known as cixutumumab. Other names used in study records include IMC-A12 (cixutumumab), IMC-A12 (cixutumumab) - 20 mg/kg, and IMC-A12-kg. These all refer to the same investigational monoclonal antibody developed by Eli Lilly and Company.