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

NCT ID: NCT02807844

Last Updated: 2021-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-29
• Study Completion Date: 2020-06-04

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ph Ib: MCS110 1 mg/kg Q3W + PDR001 100 mg Q3W

Phase Ib: MCS110 1 mg/kg every 3 weeks (Q3W) + PDR001 100 mg Q3W

Group Type: EXPERIMENTAL

MCS110

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

PDR001

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Ph Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W

Phase Ib: MCS110 3 mg/kg Q3W + PDR001 100 mg Q3W

Group Type: EXPERIMENTAL

MCS110

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

PDR001

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Ph Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W

Phase Ib: MCS110 3 mg/kg Q3W + PDR001 300 mg Q3W

Group Type: EXPERIMENTAL

MCS110

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

PDR001

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Ph Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W

Phase Ib: MCS110 5 mg/kg Q3W + PDR001 300 mg Q3W

Group Type: EXPERIMENTAL

MCS110

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

PDR001

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Ph Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W

Phase Ib: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W

Group Type: EXPERIMENTAL

MCS110

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

PDR001

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Ph Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W

Phase Ib: MCS110 10 mg/kg Q3W + PDR001 300 mg Q3W

Group Type: EXPERIMENTAL

MCS110

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

PDR001

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - TNBC

Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Triple negative breast cancer (TNBC)

Group Type: EXPERIMENTAL

MCS110

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

PDR001

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - PC

Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Pancreatic cancer (PC)

Group Type: EXPERIMENTAL

MCS110

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

PDR001

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - EC

Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Endometrial cancer (EC)

Group Type: EXPERIMENTAL

MCS110

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

PDR001

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Ph II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - ME

Phase II: MCS110 7.5 mg/kg Q3W + PDR001 300 mg Q3W - Melanoma (ME)

Group Type: EXPERIMENTAL

MCS110

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

PDR001

Intervention Type: DRUG

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Interventions

MCS110

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Intervention Type: DRUG

PDR001

MCS110 and PDR001 - for administration once every 3 weeks via i.v. infusion.

Intervention Type: DRUG

Other Intervention Names

colony-stimulating factor-1 [CSF-1])

Eligibility Criteria

Inclusion Criteria

• Signed informed consent prior to any procedures
• Phase Ib part: Adult patients with advanced melanoma, endometrial carcinoma, pancreatic or TNBC, with measurable or non-measurable disease who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
• Phase II part: Adult patients with advanced solid tumors who have received standard therapy (no more than 3 prior lines of treatment) or are intolerant of standard therapy, have progressed following their last prior therapy, and fit into one of the following groups:

• Group 1: TNBC who did not receive prior anti-PD-1/PD-L1 treatment
• Group 2: Pancreatic adenocarcinoma who did not receive prior anti-PD-1/PD-L1 treatment
• Group 3: Endometrial carcinoma who did not receive prior anti-PD-1/PD-L1 treatment
• Group 4: Melanoma who progressed on prior anti-PD-1/PD-L1 treatment.

Exclusion Criteria

• Patients with the following:

• Symptomatic central nervous system (CNS) metastases or those requiring local CNS-directed therapy.
• Abnormal liver, renal, or blood lab values.
• Impaired cardiac function or clinically significant cardiac disease.
• Active autoimmune disease or documented autoimmune disease within 3 years of screening.
• Active infection requiring antibiotic therapy.
• Known HIV, active hepatitis B or C virus.
• Concurrent malignant disease.
• Patients who received systemic anticancer therapy, major surgery, or radiotherapy within 2 weeks of study treatment, or live vaccines within 4 weeks of study treatment.
• Patients requiring chronic treatment with systemic steroid therapy or any immunosuppressive therapy.
• Patients who used hematopoietic colony-stimulating growth factors within 2 weeks of study treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Dana Farber Cancer Center

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

The West Clinic

Germantown, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Novartis Investigative Site

Wilrijk, , Belgium

Novartis Investigative Site

HUS, , Finland

Novartis Investigative Site

Saint-Herblain, , France

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Ulm, , Germany

Novartis Investigative Site

Hong Kong, , Hong Kong

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Koto Ku, Tokyo, Japan

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Valencia, Valencia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Chur, , Switzerland

Novartis Investigative Site

Geneva, , Switzerland

Novartis Investigative Site

Zurich, , Switzerland

Countries

United States; Belgium; Finland; France; Germany; Hong Kong; Italy; Japan; South Korea; Spain; Switzerland

References

Ahmed J, Stephen B, Yang Y, Kwiatkowski E, Ejezie CL, Pant S. Phase Ib/II Study of Lacnotuzumab in Combination with Spartalizumab in Patients with Advanced Malignancies. J Immunother Precis Oncol. 2024 May 2;7(2):73-81. doi: 10.36401/JIPO-23-16. eCollection 2024 May.

Reference Type: DERIVED

PMID: 38721402 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-000210-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CMCS110Z2102

Identifier Type: -

Identifier Source: org_study_id