Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as OMP-21M18
Demcizumab · 7 trials · 6 indications
Investigator assessed Kaplan-Meier estimates of progression-free survival for placebo/placebo arm and pooled demcizumab arm.
Investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response rate (unconfirmed) in placebo/placebo arm to demcizumab/placebo arm and demcizumab/demcizumab arm combined in subjects with first-line stage IV non-small cell lung cancer (NSCLC). Response rate was based on Investigator-assessed best-overall-response (BOR) and was defined as the best unconfirmed response determined by RECIST version 1.1 recorded from the start of the treatment until disease progression in the following order of importance: CR, PR , SD, progressive disease (PD), not evaluable, or missing.
The maximum tolerated dose (MTD) or maximum administered dose (MAD) will be determined in patients treated with demcizumab in combination with pembrolizumab
| Arm | Type | Description |
|---|---|---|
| Abraxane® and gemcitabine plus placebo | EXPERIMENTAL | Abraxane® and gemcitabine plus placebo (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression |
| Abraxane® and gemcitabine plus demcizumab plus placebo | EXPERIMENTAL | Abraxane® and gemcitabine plus demcizumab (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression |
| Abraxane® and gemcitabine plus demcizumab | EXPERIMENTAL | Abraxane® and gemcitabine plus demcizumab (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus demcizumab (3 cycles) and then Abraxane® and gemcitabine until disease progression |
| Arm 1 Pem, carbo, placebo x 4 cycles | PLACEBO_COMPARATOR | Pemetrexed (500 mg/m2),carboplatin (area under the concentration-time curve of 6 mg/mL x min) once every 21 days X 4 cycles, pemetrexed maintenance and placebo starting at Day 84 |
| Arm 2 Pem, carbo x 4 cycles, one course of dem | ACTIVE_COMPARATOR | Pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve of 6 mg/mL x min) x 4 cycles, one course of demcizumab 5mg/kg, maintenance pemetrexed + placebo starting on Day 84 |
| Arm 3 pem, carbo, dem x 4 cycles, dem retreatment | ACTIVE_COMPARATOR | Pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve of 6 mg/mL x min) x 4 cycles, maintenance pemetrexed starting on Day 84. 2 courses of demcizumab 5 mg/kg |
| Demcizumab and Pembrolizumab | EXPERIMENTAL | Demcizumab will be administered prior to pembrolizumab |
| Carboplatin and Pemetrexed plus demcizumab | EXPERIMENTAL | Carboplatin and Pemetrexed plus demcizumab |
| Pemetrexed plus demcizumab | EXPERIMENTAL | Pemetrexed plus demcizumab |
| Gemcitabine and demcizumab With or Without Abraxane® | EXPERIMENTAL | Gemcitabine and demcizumab With or Without Abraxane® |
| Open-label OMP-21M18 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Demcizumab | DRUG | administered intravenously |
| Abraxane® | DRUG | administered intravenously |
| gemcitabine | DRUG | administered intravenously |
| Placebo | DRUG | - |
| Pemetrexed | DRUG | - |
| Carboplatin | DRUG | - |
| Pembrolizumab | DRUG | Drug: Pembrolizumab administered 2mg/kg IV every 3 weeks |
| OMP-21M18 | DRUG | The first 6 participants will receive OMP21M18 2.5 mg/kg once every other week, the next 6 participants will receive 5 mg/kg once every other week, and the final 6 participants will receive 10 mg/kg once every other week. A Data Safety Monitoring Board (DSMB) will review the data for the 6 participants in each dose level after the last participant in that group has been treated for 56 days and decide whether it is safe to move up to the next highest dose level. After confirming the optimum dose, 14 additional participants will be treated at the highest dose level that the DSMB considers safe. |
Inclusion Criteria: 1. Subjects must have histologically confirmed metastatic pancreatic ductal adenocarcinoma.. Prior chemotherapy and/or radiotherapy either in the adjuvant or neoadjuvant setting or for metastatic disease is not allowed. 2. Availability of formalin-fixed paraffin-embedded (FFPE) ...
Demcizumab is an investigational monoclonal antibody being studied in oncology for locally advanced or metastatic solid tumors, non-small cell lung cancer, nonsquamous non-small cell lung cancer, and pancreatic cancer. It has been evaluated in completed clinical trials in these indications, including first-line metastatic pancreatic ductal adenocarcinoma and non-squamous non-small cell lung cancer.
Demcizumab targets DLL4, a ligand in the Notch signaling pathway. It is classified as an inhibitor of DLL4. By binding DLL4, the antibody is designed to interfere with DLL4-mediated signaling, which is a mechanism explored in oncology drug development. Demcizumab is a monoclonal antibody modality.
Demcizumab is being developed by Mereo BioPharma Group plc, which trades under the ticker MREO. The company is the sponsor associated with the clinical development program for this monoclonal antibody across the solid tumor and lung and pancreatic cancer indications studied.
Demcizumab is in Phase 1 development and remains investigational. Its clinical program includes Phase 1 and Phase 2 studies, all of which are completed, with no active trials. The studies enrolled a total of 264 participants across the solid tumor, non-small cell lung cancer, and pancreatic cancer settings.
Demcizumab has been studied in completed trials including NCT02722954, a Phase 1b study with pembrolizumab in locally advanced or metastatic solid tumors, and NCT02289898, a Phase 2 study in first-line metastatic pancreatic ductal adenocarcinoma. Other completed studies include NCT02259582 and NCT01189968 in non-squamous non-small cell lung cancer.
Yes, Demcizumab is also known as OMP-21M18. The earlier clinical study NCT01189968 lists the drug as Demcizumab (OMP-21M18), confirming that both names refer to the same monoclonal antibody developed by Mereo BioPharma Group plc.