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Also known as MM-121 (SAR256212), SAR256212
MM-121 · 4 trials · 7 indications
Pathologic Complete Response was defined as the absence of invasive cancer in the breast and lymph nodes following completion of neoadjuvant systemic therapy and reported according to the current AJCC staging system for neoadjuvant clinical studies. The endpoint was to determine the pathologic Complete Response (pCR) rates associated with weekly treatment of MM-121 plus paclitaxel followed by the combination treatment of doxorubicin plus cyclophosphamide compared with weekly paclitaxel alone followed by the combination treatment of doxorubicin plus cyclophosphamide in patients with human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer.
Safety and tolerability data presented in detail in the adverse events and serious adverse events section of the results posting
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8 Pemetrexed doses tested: 500 mg/m2 Day 1 Carboplatin doses tested: 5 or 6 AUC Day 1 Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8
Maximum Tolerated Dose reported in Target AUC, as calculated by the Calvert Formula Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Carboplatin doses tested: 5 or 6 AUC Day 1
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Pemetrexed doses tested: 500 mg/m2 Day 1
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3
To establish the safety of escalating doses of MM-121 administered in combination with multiple anti-cancer therapies in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD to be used for the expansion cohort. DLTs were not measured in the Expansion Cohort.
To establish the safety of escalating doses of MM-121 in combination with paclitaxel in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD.
Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. Part 1 Cohort 1: MM-121: 20 mg/kg loading dose followed by 12 mg/kg QW IV )20/12) + Paclitaxel: 80mg/m2 IV QW Part 1 Cohort 2: MM-121: 40 mg/kg loading dose followed by 20 mg/kg QW IV (40/20) + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 1: MM-121: 40/20 mg/kg IV + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 2: MM-121 20 /12 mg/kg IV QW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 3: MM-121 40mg/kg IV QOW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 4: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest + Paclitaxel: 80mg/m2 weekly IV for 3 weeks, followed by one week of rest
Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. Part 1 Cohort 1: MM-121: 20 mg/kg loading dose followed by 12 mg/kg QW IV )20/12) + Paclitaxel: 80mg/m2 IV QW Part 1 Cohort 2: MM-121: 40 mg/kg loading dose followed by 20 mg/kg QW IV (40/20) + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 1: MM-121: 40/20 mg/kg IV + Paclitaxel: 80mg/m2 QW IV Part 2 Cohort 2: MM-121 20 /12 mg/kg IV QW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 3: MM-121 40mg/kg IV QOW + Paclitaxel: 80 mg/m2 QW IV Part 2 Cohort 4: MM-121 - 40 mg/kg loading dose followed by 20 mg/kg weekly IV for 3 weeks, followed by one week of rest + Paclitaxel: 80mg/m2 weekly IV for 3 weeks, followed by one week of rest
| Arm | Type | Description |
|---|---|---|
| MM-121 (SAR256212) + paclitaxel | EXPERIMENTAL | 2 week run-in of MM-121 followed by MM-121 + dosing of paclitaxel IV, followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery. |
| Paclitaxel only | ACTIVE_COMPARATOR | Standard dosing of paclitaxel IV, followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery. |
| MM-121 plus Gemcitabine | EXPERIMENTAL | escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle |
| MM-121 plus Carboplatin | EXPERIMENTAL | carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle |
| MM-121 plus Pemetrexed | EXPERIMENTAL | pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle |
| MM-121 plus Cabazitaxel | EXPERIMENTAL | escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle |
| dose escalation and expansion | EXPERIMENTAL | SAR245408 taken every day in the morning: no eating 2 hours prior and 1 hour after dose; SAR256212 will be given weekly by IV infusion over 1 hour, right after the SAR245408 oral dose |
| MM-121 + Paclitaxel | EXPERIMENTAL | Escalating doses of MM-121 given IV QW in combination with paclitaxel at standard dose of 80 mg/m2 IV QW |
| Name | Type | Description |
|---|---|---|
| MM-121 | DRUG | MM-121 IV at 40 mg/mg loading dose on Cycle 1, Week 1 followed by 20 mg/mg weekly for all subsequent doses |
| Paclitaxel | DRUG | Standard dosing of paclitaxel IV, followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery. |
| Carboplatin | DRUG | administered at AUC 6 |
| Pemetrexed | DRUG | administered IV at 500 mg/m2 |
| Cabazitaxel | DRUG | administered IV at 20 mg/m2 or 25 mg/m2 |
| Gemcitabine | DRUG | administered IV at 1000 mg/m2 or 1250 mg/m2 |
| MM-121 (SAR256212) | DRUG | Pharmaceutical form:solution Route of administration: Intravenous |
| SAR245408 | DRUG | Pharmaceutical form:tablet Route of administration: oral |
Inclusion Criteria: * Histological confirmation of ER positive, HER2 negative invasive breast cancer (Group 1) or invasive triple-negative breast cancer (Group 2) * Free of metastatic disease * ≥ 18 years old * Female * Had no prior treatment for any cancer * Eligible for treatment with paclitaxel,...
MM-121 is an investigational small molecule oncology drug developed by Sanofi for solid tumors and other cancers. It has been studied in ER positive, HER2 negative breast cancer, triple negative breast cancer, ovarian cancer, fallopian tube cancer, and advanced solid tumors. It is not approved and remains in clinical development.
MM-121 has been studied in ER positive, HER2 negative breast cancer and triple negative breast cancer. One Phase 2 trial, NCT01421472, evaluated preoperative MM-121 with paclitaxel in HER2-negative breast cancer patients and enrolled 196 participants. The drug is investigational and has not been approved for any breast cancer indication.
Sanofi develops MM-121, which is also known as SAR256212. Sanofi trades on the New York Stock Exchange under the ticker SNY. The drug is part of Sanofi's oncology pipeline and has been studied across multiple solid tumor types in company-sponsored clinical trials.
MM-121 is in Phase 2 clinical development. A Phase 2 trial, NCT01421472, has been completed, along with several Phase 1 studies. The drug is investigational and has not received FDA approval for any indication.
MM-121 has been evaluated in completed trials including NCT01447225, a Phase 1 study in advanced solid tumors with 43 patients, NCT01436565, a Phase 1 study in solid tumor cancers with 26 patients, NCT01421472, a Phase 2 breast cancer trial with 196 patients, and NCT01209195, a Phase 1 study in gynecologic and breast cancers with 41 patients.
Yes, MM-121 is also known as SAR256212. Both names refer to the same investigational small molecule developed by Sanofi. The SAR256212 designation appears in trial NCT01436565, which studied the drug in combination with SAR245408 in patients with solid tumor cancers.