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

Novartis

Status and phase: Completed; Phase 2; Phase 1

Conditions: Endometrial Carcinoma; Melanoma; Triple Negative Breast Cancer; Pancreatic Carcinoma

Treatments: Drug: MCS110; Drug: PDR001

Study type: Interventional

Funder types: Industry

Identifiers

NCT02807844

2016-000210-29 (EudraCT Number)

CMCS110Z2102

Details and patient eligibility

About

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.

Full 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).

Enrollment: 141 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Main 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.

Main 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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141 participants in 10 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: MCS110

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: MCS110

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: MCS110

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: MCS110

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: MCS110

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: MCS110

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: MCS110

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: MCS110

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: MCS110

Drug: PDR001

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

Experimental group

Description:

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

Treatment:

Drug: MCS110

Drug: PDR001