Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as LY2875358
Emibetuzumab · 6 trials · 10 indications
ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, CR was defined as the disappearance of all target and non-target lesions; PR defined as a \>30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) \* 100.
DLT is defined as an adverse event during Cycle1 that is possibly, probably, or definitely related to treatment with Emibetuzumab in combination with fixed regimen of Ramucirumab \& fulfills any 1 of the following criterion using NCI CTCAE Version 4.03: Grade 3 non-hematological toxicity. Exceptions will be made for:Nausea, vomiting, diarrhea, constipation, or skin rash that persists for ≤3 days following appropriate supportive care intervention. Grade 3 hypertension in which systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg persist \<7 days after intensified antihypertensive therapy is initiated. Grade 4 hematological toxicity of ≥7 days duration. ≥Grade 3 thrombocytopenia with ≥Grade 2 bleeding. Any febrile neutropenia. Any other significant toxicity deemed by the primary investigator \& Lilly clinical research personnel to be dose-limiting (eg, any toxicity that is possibly related to the study medication that requires the withdrawal of participant from study Cycle1).
ORR is the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
| Arm | Type | Description |
|---|---|---|
| LY2875358 plus Erlotinib | EXPERIMENTAL | Lead In: Approximately 8 weeks of erlotinib 150 milligram (mg) given orally per day. Randomization: Erlotinib 150 mg given orally per day plus 750 mg LY2875358 given as 1.5 hours intravenous (IV) infusions on Days 1 and 15 of 28-day cycles. |
| Erlotinib | ACTIVE_COMPARATOR | Lead In: Approximately 8 weeks of erlotinib 150 mg given orally per day. Randomization: Continue Erlotinib 150 mg given orally per day, in 28-day cycles. |
| Arm A: Emibetuzumab plus Erlotinib | EXPERIMENTAL | 750 milligram (mg) Emibetuzumab flat dose given as a 1.5 hour intravenous (IV) infusion on Days 1 and 15 of a 28-day cycle and Erlotinib 150 mg given orally once daily on a 28-day cycle. |
| Arm B: Emibetuzumab | EXPERIMENTAL | 750 mg Emibetuzumab flat dose given as a 1.5-hour IV infusion on Days 1 and 15 of a 28-day cycle. |
| LY2875358 | EXPERIMENTAL | LY2875358 will be administered intravenously (IV) at 2000 milligram (mg) bi-weekly in 28 day Cycle. |
| Emibetuzumab + Ramucirumab (Part A) | EXPERIMENTAL | Part A: Dose escalation (750mg, 2000mg) of Emibetuzumab administered intravenously (IV), on days 1 and 15 every 28 day cycle in combination with a fixed dose of 8mg/kg ramucirumab administered IV on Days 1 and 15 every 28 day cycle. |
| Emibetuzumab + Ramucirumab (Part B) | EXPERIMENTAL | Part B: Recommended 750mg Emibetuzumab dose from Part A to be administered IV, on days 1 and 15 every 28 day cycle in combination with a fixed dose of 8mg/kg ramucirumab administered IV on Days 1 and 15 every 28 day cycle. |
| LY2875358+Erlotinib | EXPERIMENTAL | Part B1. Erlotinib will be administered orally at 150 mg dose level each day. LY2875358 will be administered intravenously (IV) at recommended dose level in Part A on Day 1 and Day 15 of a 28-day cycle. (Part B1 was added per protocol amendment in January, 2013.) |
| LY2875358+Gefitinib | EXPERIMENTAL | Part B2. Gefitinib will be administered orally at 250 mg dose level each day. LY2875358 will be administered intravenously (IV) at recommended dose level in Part A on Day 1 and Day 15 of a 28-day cycle. (Part B2 was added per protocol amendment in January, 2013.) |
| LY2875358 + erlotinib | EXPERIMENTAL | - |
| LY2875358 at Part A highest dose | EXPERIMENTAL | - |
| LY2875358 at Part A highest dose + trametinib | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| LY2875358 | BIOLOGICAL | Administered IV |
| Erlotinib | DRUG | Administered Orally |
| Emibetuzumab | DRUG | Administered IV |
| Ramucirumab | DRUG | Administered Intravenously (IV) |
| Gefitinib | DRUG | Administered orally |
| LY2875358 + erlotinib | DRUG | Part A2 Dose escalation of LY2875358 administered IV, on Day 1 and 15 every 28 days for at least two cycles in combination with daily erlotinib dosing (150 mg) taken orally (PO). |
| LY2875358 at Part A highest dose | DRUG | Part B (Dose Exploration): LY2875358 at Part A highest dose administered IV, on Day 1 and 15 every 28 days for at least two cycles. |
| LY2875358 at Part A highest dose + trametinib | DRUG | Part B (in combination with trametinib): LY2875358 at Part A highest dose administered IV, on Day 1 and 15 every 28 days for at least two cycles, in combination with trametinib at 2 mg orally once daily |
Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of metastatic Stage IV NSCLC * Have at least 1 measurable lesion whose presence is assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) * Have molecular evidence of an epid...
Emibetuzumab is an investigational monoclonal antibody that has been studied in advanced cancer, including non-small cell lung cancer, gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, hepatocellular cancer, and renal cell carcinoma. It is not an approved therapy and remains in clinical development. Eli Lilly and Company is the developer.
Emibetuzumab targets MET, a receptor tyrosine kinase. It is a monoclonal antibody that acts as an inhibitor of MET signaling. Because MET is a molecular target supplied for this asset, the drug is designed to interfere with MET-mediated pathways in cancer cells.
Emibetuzumab is developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. Lilly is the sponsor of the clinical studies conducted with the agent in advanced cancer and non-small cell lung cancer.
Emibetuzumab is in Phase 1 clinical development according to the development stage recorded for the asset, and it is investigational. It has not been approved by the FDA. The clinical program includes a completed Phase 1 study and a completed Phase 2 study in non-small cell lung cancer.
Emibetuzumab has been evaluated in NCT02082210, a completed Phase 1 study of emibetuzumab combined with ramucirumab in participants with advanced cancer, and NCT01900652, a completed Phase 2 study in non-small cell lung cancer. Both trials are completed, and no trials are currently active.
The Emibetuzumab clinical program enrolled a total of 111 participants across its studies. The Phase 1 combination study NCT02082210 enrolled 97 participants, and the Phase 2 non-small cell lung cancer study NCT01900652 enrolled 111 participants.