Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
M3814 · 2 trials · 3 indications
A DLT was defined as any Grade more than or equal to \>= 3 nonhematologic Adverse Event(AE) or any Grade\>= 4 hematologic,, occurring during the DLT period that is related to any of the study interventions. In addition, a DLT is considered: Grade 3 thrombocytopenia with medically concerning bleeding, Any febrile neutropenia. A study intervention-related Treatment emergent Adverse Event(TEAE) is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk. Any toxicity related to study intervention that causes the participant to receive less than 80% of M3814 during DLT period, evidence of study treatment-related hepatocellular injury for more than 3 days, such as\> 5-fold elevations above the Upper Limits of Normal (ULN) of Alanine Aminotransferase (ALT) or Aspartate Aminotransferase(AST) with or without elevation of serum total bilirubin to \> 2 × ULN. Number of Participants with DLT Grade \>= 3 were reported.
A DLT was defined as any Grade more than or equal to \>= 3 nonhematologic Adverse Event(AE) or any Grade\>= 4 hematologic,, occurring during the DLT period that is related to any of the study interventions. In addition, a DLT is considered: Grade 3 thrombocytopenia with medically concerning bleeding, Any febrile neutropenia. A study intervention-related Treatment emergent Adverse Event(TEAE) is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk. Any toxicity related to study intervention that causes the participant to receive less than 80% of M3814 during DLT period, evidence of study treatment-related hepatocellular injury for more than 3 days, such as\> 5-fold elevations above the Upper Limits of Normal (ULN) of Alanine Aminotransferase (ALT) or Aspartate Aminotransferase(AST) with or without elevation of serum total bilirubin to \> 2 × ULN. Number of Participants with DLT Grade \>= 3 were reported.
Area under the plasma concentration versus time curve from time zero to 6 hours post dosing for M3814 was reported.
Cmax was obtained directly from the concentration versus time curve.
DLT: any Grade (Gr) greater than or equal to (\>=) 3 nonhematologic adverse event (AE)/any Gr\>=4 hematologic AE that is related to any of study treatments and occurs during the DLT period of 5 weeks (Phase Ia, Arm A) after the first dose of M3814. Following are considered as DLTs: Gr3 thrombocytopenia with medically concerning bleeding; Febrile neutropenia; Any toxicity/study treatment-related adverse event (TEAE) that, in opinion of Safety Monitoring Committee (SMC), is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk; Any toxicity related to study treatments that causes participant to receive less than 80 percent (%) of the planned RT dose; Evidence of study treatment-related hepatocellular injury for \> 3 days.
DLT: any Grade (Gr) greater than or equal to (\>=) 3 nonhematologic AE/any Gr\>=4 hematologic AE that is related to any of study treatments and occurs during the DLT period of 12 weeks (Phase Ia, Arm B) after the first dose of M3814. Following are considered as DLTs: Gr3 thrombocytopenia with medically concerning bleeding; Febrile neutropenia; Any toxicity/study treatment-related adverse event (TEAE) that, in opinion of Safety Monitoring Committee (SMC), is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk; Any toxicity related to study treatments that causes participant to receive less than 80 percent (%) of the planned RT dose; Any toxicity related to study treatments leading to an interruption of RT longer than 1 week in Arm B; Evidence of study treatment-related hepatocellular injury for \> 3 days.
| Arm | Type | Description |
|---|---|---|
| Part A: M3814 + Avelumab | EXPERIMENTAL | - |
| Part B: M3814 + Avelumab + Radiotherapy (RT) | EXPERIMENTAL | - |
| Part FE: M3814 + Avelumab (fasted/fed state) | EXPERIMENTAL | - |
| Phase 1a (Arm A): M3814 Capsule (100 mg) + RT | EXPERIMENTAL | Participants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative radiotherapy (RT) received 100 milligrams (mg) of M3814 as capsule orally once daily on fraction day (FD) 6 in combination with RT (3 Gray \[Gy\] x 10, 5 fractions per week \[F/W\]). |
| Phase 1a (Arm A): M3814 Capsule (200 mg) + RT | EXPERIMENTAL | Participants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 200 mg of M3814 as capsule orally once daily on FD 6 in combination with RT (3 \[Gy\] x 10, 5 F/W). |
| Phase 1a (Arm A): M3814 Capsule (300 mg) + RT | EXPERIMENTAL | Participants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 300 mg of M3814 as capsule orally once daily on FD 6 in combination with RT (3 \[Gy\] x 10, 5 F/W). |
| Phase 1a (Arm A): M3814 Capsule (400 mg) + RT | EXPERIMENTAL | Participants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 400 mg of M3814 as capsule orally once daily on FD 6 in combination with RT (3 \[Gy\] x 10, 5 F/W). |
| Phase 1a (Arm A): M3814 Tablet (100 mg) + RT | EXPERIMENTAL | Participants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 100 mg of M3814 as tablet orally once daily for 2 consecutive weeks in combination with RT (3 Gy x 10, 5 F/W). |
| Phase 1a (Arm A): M3814 Tablet (200 mg) + RT | EXPERIMENTAL | Participants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 200 mg of M3814 as tablet orally once daily for 2 consecutive weeks in combination with RT (3 Gy x 10, 5 F/W). |
| Phase 1a (Arm A): M3814 Tablet (300 mg) + RT | EXPERIMENTAL | Participants with locally advanced disease (any tumor or metastases including lymphomas) localized in the head and neck region or thorax that was not amenable to surgical therapy, or with standard systemic therapy with an indication for palliative RT received 300 mg of M3814 as tablet orally once daily for 2 consecutive weeks in combination with RT (3 Gy x 10, 5 F/W). |
| Phase 1a (Arm B): M3814 Capsule (50 mg) + CRT | EXPERIMENTAL | Participants with local/locally advanced squamous cell carcinoma of the head and neck (SCCHN) received 50 mg of M3814 as capsule orally once daily on FD 6 in combination with fractionated RT (2 Gy x 33 to 35 fractions; 5 F/W) and Cisplatin twice at a dose of 100 milligrams per square meter (mg/m\^2) or weekly at a dose of 40 (mg/m\^2). |
| Phase 1a (Arm B): M3814 Tablet (100 mg) + CRT | EXPERIMENTAL | Participants with squamous cell carcinoma of the head and neck (SCCHN) received 100 mg of M3814 as tablet orally once daily for 7 consecutive weeks in combination with fractionated RT (2 Gy X 33 to 35 fractions; 5 F/W) and Cisplatin twice at a dose of 100 mg/m\^2 or weekly at a dose of 40 (mg/m\^2). |
| Ancillary cPoP: M3814 Capsule (100 mg) + RT | EXPERIMENTAL | Participants with at least 2 (sub)cutaneous tumor/metastases of any type (at least 2 centimeters \[cm\] apart) with an indication for single high dose-palliative RT were included and received single oral dose of M3814 capsule at a dose of 100 mg on Day 2, prior 1.5 hours start of RT and a single high dose of RT (10-25 Gy) on Lesion 1 on Day 1 and on Lesion 2 on Day 2. |
| Ancillary cPOP: M3814 Capsule (200 mg) + RT | EXPERIMENTAL | Participants with at least 2 (sub)cutaneous tumor/metastases of any type (at least 2 cm apart) with an indication for single high dose-palliative RT were included and received single oral dose of M3814 capsule at a dose of 200 mg on Day 2, prior 1.5 hours start of RT and a single high dose of RT (10-25 Gy) on Lesion 1 on Day 1 and on Lesion 2 on Day 2. |
| Ancillary cPOP: M3814 Capsule (400 mg) + RT | EXPERIMENTAL | Participants with at least 2 (sub)cutaneous tumor/metastases of any type (at least 2 cm apart) with an indication for single high dose-palliative RT were included and received single oral dose of M3814 capsule at a dose of 400 mg on Day 2, prior 1.5 hours start of RT and a single high dose of RT (10-25 Gy) on Lesion 1 on Day 1 and on Lesion 2 on Day 2 |
| Name | Type | Description |
|---|---|---|
| M3814 | DRUG | Participants received M3814 twice daily (BID) continuously starting from Day 1 until progressive disease (PD) or unacceptable toxicity. |
| Avelumab | DRUG | Participants received avelumab once every 2 weeks (Q2W) starting from Day 1 until PD or unacceptable toxicity. |
| Radiotherapy | RADIATION | Participants received radiotherapy at the dose of 3 grays (Gy) per day starting Day 1 for 5 days per week for 2 weeks. |
| M3814 100 mg | DRUG | Participants received 100 mg of M3814 as capsule or tablet orally once daily. |
| M3814 200 mg | DRUG | Participants received 200 mg of M3814 as capsule or tablet orally once daily. |
| M3814 300 mg | DRUG | Participants received 300 mg of M3814 as capsule or tablet orally once daily. |
| M3814 400 mg | DRUG | Participants received 400 mg of M3814 as capsule or tablet orally once daily. |
| M3814 50 mg | DRUG | Participants received 100 mg of M3814 as capsule orally once daily. |
| Fractionated RT | RADIATION | Participants received fractionated palliative RT (3 Gray \[Gy\] \* 10 in Arm A and 2 Gy \* 33 to 35, 5 fractions per week \[F/W\]) in Arm B and received a single high dose of RT (10-25 Gy) capsule on Day 1 given on Lesion 1 and a single high dose of RT (10-25 Gy) on Day 2 given on Lesion 2 in ancillary CPoP part. |
| Cisplatin | DRUG | Participants received Cisplatin twice at a dose of 100 mg/m\^2 or weekly at a dose of 40 mg/m\^2. |
Inclusion Criteria: * Part A and Part FE (M3814 + avelumab): Participants had histologically or cytologically proven advanced or metastatic solid tumors for which no standard therapy exists, standard therapy has failed, or participants are intolerant to or have rejected established therapy known to...
| 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 |
M3814 is an investigational small molecule being studied for the treatment of advanced solid tumors. It has been evaluated in Phase 1 clinical trials, including in combination with radiotherapy and with avelumab, for patients with advanced solid tumors and other oncology indications.
M3814 is being developed by Merck KGaA, a biopharmaceutical company. The company's ticker symbol is MKGAF. Merck KGaA has sponsored clinical trials to evaluate M3814 in patients with advanced solid tumors.
M3814 is in Phase 1 clinical development. It has completed two Phase 1 trials, one testing it in combination with radiotherapy and another testing it in combination with avelumab. M3814 is investigational and not yet approved by regulatory authorities.
M3814 has been studied in two completed Phase 1 trials. NCT02516813 evaluated M3814 in combination with radiotherapy in patients with advanced solid tumors. NCT03724890 evaluated M3814 in combination with avelumab in patients with solid tumors. Both trials are now completed.
Yes, M3814 is also known as MSC2490484A. The clinical trial NCT02516813, which studied M3814 in combination with radiotherapy, used the name MSC2490484A in its title. Both names refer to the same investigational drug.