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Demcizumab · 5 trials · 4 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® |
| 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 |
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 developed by Mereo BioPharma Group plc for the treatment of solid tumors. It has been studied in locally advanced or metastatic solid tumors, non-small cell lung cancer, and pancreatic cancer. It is not an approved therapy and remains in clinical development.
Demcizumab targets DLL4, a ligand in the Notch signaling pathway. It acts as an inhibitor of DLL4. By binding DLL4, the antibody is designed to interfere with Notch pathway signaling, which is involved in tumor blood vessel formation and cancer stem cell biology. This mechanism is being explored in oncology.
Demcizumab is being developed by Mereo BioPharma Group plc, which trades under the ticker MREO. The company holds the development program for this monoclonal antibody across its oncology indications, including non-small cell lung cancer and pancreatic cancer.
Demcizumab is in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA or any other regulatory authority. The program has included both Phase 1 and Phase 2 studies, all of which are now completed, with no active trials currently listed.
Demcizumab has been evaluated in completed studies including NCT02722954, a Phase 1b trial combining it with pembrolizumab in locally advanced or metastatic solid tumors, and NCT02289898, a Phase 2 trial in first-line metastatic pancreatic ductal adenocarcinoma. Other completed trials include NCT02259582 and NCT01189968 in non-small cell lung cancer.
Demcizumab has been studied in pancreatic cancer, specifically first-line metastatic pancreatic ductal adenocarcinoma. In the completed Phase 2 trial NCT02289898, it was evaluated in combination with gemcitabine and Abraxane compared with placebo. It is investigational and not approved for use in pancreatic cancer or any other indication.