NCT02807844

Phase Ib/II Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies

A Phase Ib/II, Open Label, Multicenter Study of MCS110 in Combination With PDR001 in Patients With Advanced Malignancies

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 141 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study of MCS110 with PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the combination of MCS110 with PDR001 in adult patients with solid tumors.

Detailed description

Combined treatment with MCS110 and PDR001 was expected to result in Tumor-associated macrophages (TAM) depletion, enhanced T-cell activation and synergistic antitumor activity in the clinical setting. This study was a Phase Ib/II, multi-center, open label study starting with a Phase Ib dose escalation part followed by a Phase II part. MCS110 and PDR001 were administered i.v. Q3W until the patient experienced unacceptable toxicity, progressive disease as per irRC and/or treatment was discontinued at the discretion of the investigator or the patient. Patients were not to discontinue treatment based on progressive disease per Response evaluation criteria in solid tumors (RECIST) v1.1. During the Phase Ib part of the study, cohorts of patients were treated with increasing doses of MCS110 and PDR001 every 3 weeks until a Recommended Phase 2 Dose (RP2D) was determined for this treatment combination. To assure that the combination RP2D did not exceed the Maximum tolerated dose (MTD), the combination MCS110 and PDR001 dose escalation was guided by a Bayesian logistic regression model (BLRM) with overdose control (EWOC) principle based on dose limiting toxicity data in the context of available safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) information. Once the MTD and/or RP2D was declared, additional patients were enrolled in the Phase II part in order to assess the preliminary anti-tumor activity of MCS110 in combination with PDR001 in anti-PD1/PD-L1-naive triple negative breast cancer (TNBC), pancreatic (PC), endometrial carcinoma (EC) and anti PD1/PD-L1-resistance melanoma (ME).

Conditions

• Triple Negative Breast Cancer
• Pancreatic Carcinoma
• Melanoma
• Endometrial Carcinoma

Interventions

Type	Name	Description
DRUG	MCS110	MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.
DRUG	PDR001	MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Timeline

• Start date: 2016-06-29
• Primary completion: 2020-06-04
• Completion: 2020-06-04
• First posted: 2016-06-21
• Last updated: 2021-08-11
• Results posted: 2021-08-11

Locations

20 sites across 11 countries: United States, Belgium, Finland, France, Germany, Hong Kong, Italy, Japan, South Korea, Spain, Switzerland

Regulatory

• FDA-regulated drug study