Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
M6620 · 3 trials · 5 indications
DLT: any death not clearly due to underlying disease/extraneous causes/Grade(Gr) \>=3 nonhematologic/Gr\>=4 hematologic toxicity that was probably/definitely related to any of study interventions, individually/combination that occurred during DLT observation period, except for any of following: Gr3 infusion-related reaction; Transient (\<=6hr) Gr3 flu-like symptoms/fever, controlled with medical management; Transient (\<=72hr) Gr3 fatigue, local reactions, headache, nausea/emesis; Gr3 diarrhea, skin toxicity, liver function test increase; Single laboratory values out of normal range and controlled with medical management; Tumor flare phenomenon: local pain, irritation/rash, localized at sites of known/suspected tumor; Neutropenia (Gr3/4) for \<7 days not associated with any infection; Gr3 thrombocytopenia for \<7 days without clinically significant bleeding and not requiring platelet transfusion; Symptomatic thyroid dysfunction manageable with treatment.
To determine the best tolerated M6620 (Berzosertib) treatment schedule (or phase II recommended dose, RPTD) administered concomitantly with radiotherapy (RT) only in the palliative treatment of oesophageal cancer.
To determine the best tolerated M6620 (Berzosertib) treatment schedule (or phase II recommended dose, RPTD) administered concomitantly with chemotherapy (cisplatin and capecitabine) only in the palliative treatment of solid cancer.
Highest treatment schedule resulting in less than 45% dose limiting toxicity (DLT) rate.
| Arm | Type | Description |
|---|---|---|
| Part A: Carboplatin + M6620 + Avelumab | EXPERIMENTAL | - |
| Stage A1, A2 & B | EXPERIMENTAL | The trial is a single arm study. Different populations are recruited to each stage and the stages run independently of each other. Stage A1 \& A2 will commence before Stage B so that safety data can be obtained in the palliative setting prior to Stage B commencing. Stage A1 may be ongoing when Stage B begins. Each Stage has a separate eligibility criteria. Stage A1: M6620 \& palliative radiotherapy Stage A2: M6620 \& palliative chemotherapy (Cisplatin \& Capecitabine) Stage B: M6620 \& definitive chemoradiotherapy |
| Part A | EXPERIMENTAL | This part will be 3 + 3 dose escalation study of M6620 in combination with gemcitabine as well as gemcitabine and cisplatin in participants with advanced solid tumors. |
| Part B | EXPERIMENTAL | This part will be 3 + 3 dose escalation study of M6620 in combination with cisplatin or cisplatin and etoposide in participants with advanced solid tumors. |
| Part B2 | EXPERIMENTAL | This part will be 3 + 3 dose escalation study of M6620 in combination with irinotecan in participants with advanced solid tumors. |
| Part C1 | EXPERIMENTAL | This will be the expansion part of the study in which participants with advanced non-small cell lung cancer (NSCLC) will be administered M6620 in combination with gemcitabine. |
| Part C2 | EXPERIMENTAL | This will be the expansion part of the study in which participants with advanced triple negative breast cancer (TNBC) will be administered M6620 in combination with cisplatin. |
| Part C3 | EXPERIMENTAL | This will be the expansion part of the study in which participants with platinum-resistant advanced small cell lung cancer (SCLC) will be administered M6620 in combination with cisplatin or carboplatin. |
| Name | Type | Description |
|---|---|---|
| M6620 | DRUG | Participants received 90 milligrams per square meter (mg/m\^2) of M6620, intravenously (IV) on Day 2 of every 3 weeks (Q3W) cycle for a maximum of 6 cycles in combination treatment with carboplatin and avelumab on Day 1. The M6620 dose may be de-escalated to 60 mg/m\^2, or 40 mg/m\^2. |
| Avelumab | DRUG | Participants received IV infusion of avelumab 1600 mg on Day 1 of each Q3W cycle for maximum of 6 cycles in combination treatment with carboplatin and M6620. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death. |
| Carboplatin | DRUG | Participants received carboplatin area under the concentration-time curve 5 on Day 1 of each Q3W cycle for a maximum of 6 cycles in combination treatment with avelumab and M6620. |
| Cisplatin | DRUG | Cisplatin is a platinum based chemotherapy drug licensed to treat a number of different types of cancer. Cisplatin use is not considered standard practice in Stage A2 \& B, therefore Cisplatin is considered an investigational medicinal product for the purpose of this trial. |
| Capecitabine | DRUG | Capecitabine is a chemotherapy drug licensed to treat a number of different types of cancer, it is a noncytotoxic pre-cursor of the cytotoxic 5-fluourouracil. Capecitabine use is not considered standard practice in Stage A2 \& B, therefore Capecitabine is considered an investigational medicinal product for the purpose of this trial. |
| Radiotherapy | RADIATION | Stage A1 uses palliative radiotherapy. Stage B uses definitive radiotherapy. |
| Gemcitabine | DRUG | - |
| Etoposide | DRUG | - |
| Irinotecan | DRUG | - |
Inclusion Criteria: * Female participants with recurrent epithelial ovarian cancer who have disease progression following maintenance treatment with a PARPi as defined below: 1. Participant must have histologically diagnosed epithelial ovarian, primary peritoneal, or fallopian tube cancer, with ...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 2 | PHASE2 | pembrolizumab |
| Incyte Corporation | INCY | 1 | PHASE2 | Chemotherapy, Retifanlimab |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | E7 TCR-T cells, Aldesleukin |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115, pembrolizumab |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
M6620 is an investigational small molecule being studied for the treatment of oesophageal adenocarcinoma, ovarian cancer, and advanced solid tumors. It is currently in Phase 1 clinical development and has not been approved by regulatory authorities.
M6620 is a small molecule that targets the ATR kinase, a key regulator of the DNA damage response. By inhibiting ATR, M6620 may enhance the effects of DNA-damaging agents and potentially overcome resistance to PARP inhibitors in certain cancers.
M6620 is being developed by Merck KGaA, a pharmaceutical company headquartered in Germany. The company's stock is traded over-the-counter under the ticker symbol MKGAF.
M6620 is in Phase 1 clinical development. All three clinical trials listed for M6620 are Phase 1 studies and have been completed. The drug remains investigational and is not yet approved for any indication.
M6620 has been studied in three completed Phase 1 trials: NCT02157792, a first-in-human study in advanced solid tumors; NCT03641547, testing M6620 plus standard treatment in oesophageal and other cancers; and NCT03704467, a study of carboplatin plus M6620 and avelumab in PARP inhibitor-resistant ovarian cancer.
Yes, M6620 is also known as berzosertib. This alternative name may be used in scientific literature and clinical trial registries, so readers searching for berzosertib will find the same investigational drug.