Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
MCS110 · 3 trials · 11 indications
PFS Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design.
To assess the efficacy of a single i.v. dose of MCS110 in changing the size of PVNS tumors (as compared to baseline) compared to placebo over 4 weeks evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients 4 weeks after receiving the first dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called "ABC4".
To assess the efficacy of a single i.v. dose of MCS110 in percent change of the PVNS tumor volume at week 4 as compared to baseline and compared to placebo evaluated by volume of PVNS tumors by 3-dimensional MRI. This analysis includes all data from patients who received at least a single dose of MCS110 (3, 5 or 10 mg/kg) or placebo and assesses the tumor volume changes at week 4 as compared to baseline. As all parts (Part A, B and C) of the study are assessed after a single dose at week 4 the data set is called "ABC4".
Assessment of maximum efficacy (multiple i.v.monthly doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 \& 10 mg/kg or 5 \& 10 mg/kg in changing PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Analysis included data starting from 1st dose of MCS110 in all treatment groups of Parts B and C. Part B patients who received placebo as 1st dose, measurement prior to receiving first dose of MCS110, was used as baseline and assessment time-points were adjusted accordingly. For Part C, participants starting treatment with low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and tumor volume reduction was ≤ 45%. Analysis includes data from patients who received at least 2 doses. The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\]
To assess the maximum efficacy of multiple monthly i.v. doses (2 to 6) of 3, 5 or 10 mg/kg MCS110 or 3 and 10 mg/kg or 5 and 10 mg/kg by percent change in the PVNS tumor volume (as compared to baseline) up to 8 weeks post last dose evaluated by MRI. Subjects starting treatment with a low dose of MCS110 of 3 or 5 mg/kg could switch to 10 mg/kg after 3 monthly doses, if MCS110 was well tolerated and the tumor volume reduction was ≤ 45%. This analysis includes data from all participants who received at least 2 doses of MCS110 and thus includes only patients from Part B and C of the study, thus the data set is called "Part BC". The following five groups were assessed: Subjects receiving only 3 mg/kg, only 5 mg/kg or 10 mg/kg and those who switched after 3 doses of 3 mg/kg to 10 mg/kg \[3/10 mg/kg\] or after 3 doses of 5 mg/kg to 10 mg/kg \[5/10 mg/kg\].
Overall incidence of Adverse Events
Phase Ib: To characterize the safety and tolerability of MCS110 in combination with PDR001 in patients with advanced solid malignancies and to identify a recommended dose combination for Phase II.
Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)
Overall Response Rate (ORR) is defined as the proportion of patients with a best overall response assessed by CT scan or MRI of complete response (CR), disappearance of all measurable and non-measurable lesions or partial response (PR), at least a 30% decrease in the sum of diameter of all measurable lesions, taking as reference the baseline sum of diameters,. based on local Investigator assessment, as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) - mean (FAS)
Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) \> 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1
Phase II: Clinical Benefit Rate (Complete response (CR) or Partial response (PR) or Stable disease (SD) \> 4 month)) per investigator based on Response evaluation criteria in solid tumors (RECIST) v1.1
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for MCS110 is cumulative planned dose (mg/kg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/kg/3wks)/planned dose intensity (mg/kg/3wks).
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Planned dose intensity for PDR001 (mg/3wks) is planned cumulative dose (mg)/ number of doses scheduled per protocol during treatment period (i.e., this is equivalent to planned dose level).
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II. Relative dose intensity (%) is 100 × dose intensity (mg/3wks)/planned dose intensity (mg/3wks).
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
To characterize the tolerability of MCS110 given in combination with PDR001 and to identify a recommended dose combination for Phase II.
Phase Ib: Dose limiting toxicities occurring during the first 2 cycles by system organ class, preferred term and maximum grade for Phase Ib. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 4.03 was used for all grading.
| Arm | Type | Description |
|---|---|---|
| Arm 1: MCS110+carboplatin+gemcitabine | EXPERIMENTAL | MCS110+carboplatin+gemcitabine |
| Arm 2: carboplatin+gemcitabine | ACTIVE_COMPARATOR | carboplatin+gemcitabine |
| MCS110 | EXPERIMENTAL | Participants will receive a single dose of 10mg/kg on day 1 administered by regular infusion. |
| Placebo | PLACEBO_COMPARATOR | Part A: single-dose placebo to match MCS110 (10 mg/kg, 1 h i.v. infusion) Part B: single dose placebo to match MCS110 (10 mg/kg, 1 h i.v. infusion administered i.v. at Day 1, followed by 6 doses of placebo to match MCS110 (10 mg/kg) |
| MCS110 3 mg/kg | EXPERIMENTAL | Part C: MCS110 3 mg/kg (i.v. infusion) |
| MCS110 5 mg/kg | EXPERIMENTAL | Part C: MCS110 5 mg/kg (i.v. infusion) |
| MCS110 10 mg/kg | EXPERIMENTAL | Part C: MCS110 10 mg/kg (i.v. infusion) |
| MCS110 3 mg/kg & MCS110 10mg/kg | EXPERIMENTAL | Part C: MCS110 3 mg/kg (i.v. infusion) \& MCS110 10 mg/kg (i.v. infusion) |
| MCS110 5 mg/kg & MCS110 10mg/kg | EXPERIMENTAL | Part C: MCS110 5 mg/kg (i.v. infusion) \& MCS110 10 mg/kg (i.v. infusion) |
| Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W | EXPERIMENTAL | Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W |
| Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W | EXPERIMENTAL | Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W |
| Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W | EXPERIMENTAL | Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W |
| Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W | EXPERIMENTAL | Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W |
| Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W | EXPERIMENTAL | Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W |
| Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W | EXPERIMENTAL | Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC | EXPERIMENTAL | Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC) |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC | EXPERIMENTAL | Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC) |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC | EXPERIMENTAL | Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC) |
| Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME | EXPERIMENTAL | Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME) |
| Name | Type | Description |
|---|---|---|
| MCS110 | DRUG | taken by I.V |
| carboplatin | DRUG | taken by I.V |
| gemcitabine | DRUG | taken by I.V |
| Placebo | DRUG | Participants will receive a single dose of NaCl on day 1 through intravenous infusion. |
| PDR001 | DRUG | MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion. |
Inclusion Criteria: * Adult women (≥ 18 years of age) with advanced TNBC. * Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) Breast Cancer by local laboratory testing, based ...
MCS110 is an investigational small molecule being studied for advanced triple negative breast cancer (TNBC) with high TAMs, pigmented villonodular synovitis (PVNS), and triple negative breast cancer. It has been evaluated in Phase 2 clinical trials for these conditions, including in combination with chemotherapy for advanced TNBC.
MCS110 is being developed by Novartis AG, a global pharmaceutical company traded on the New York Stock Exchange under the ticker NVS. Novartis has sponsored clinical trials of MCS110 in oncology indications, including triple negative breast cancer and pigmented villonodular synovitis.
MCS110 is an investigational drug that has completed Phase 2 clinical trials. It has not been approved by the FDA and remains in clinical development. Completed trials include a Phase 2 study in pigmented villonodular synovitis and a Phase 2 study in advanced triple negative breast cancer.
MCS110 has been studied in three completed clinical trials. NCT01643850 was a Phase 2 study in pigmented villonodular synovitis with 36 participants. NCT02435680 was a Phase 2 study of MCS110 with carboplatin and gemcitabine in advanced triple negative breast cancer with 50 participants. NCT02807844 was a Phase 1b/II study of MCS110 with PDR001 in advanced malignancies with 141 participants.
Yes, MCS110 has been studied in triple negative breast cancer. A Phase 2 trial (NCT02435680) evaluated MCS110 given with carboplatin and gemcitabine in advanced triple negative breast cancer with high TAMs, enrolling 50 female participants. Another trial (NCT02807844) included triple negative breast cancer among its advanced malignancy indications.
Yes, MCS110 has been studied in pigmented villonodular synovitis (PVNS). A Phase 2 clinical trial (NCT01643850) evaluated MCS110 in patients with PVNS, including giant cell tumor of the tendon sheath and tenosynovial giant cell tumor. The trial enrolled 36 participants in the United States and Switzerland.