A Study to Evaluate Safety and Therapeutic Activity of RO6874281 in Combination with Pembrolizumab, in Participants with Advanced or Metastatic Melanoma

NCT03875079 | Completed Phase 1 FDA Drug

• 2 other identifiers: BP410542018-003872-11
• Study Type: interventional
• Target: 83
• Locations: 7 countries
• Sites: 23

Brief Summary

This is an open-label, multicenter, Phase Ib study to evaluate the safety and therapeutic activity of RO6874281 in combination with pembrolizumab. The study will consist of 3 parts: a safety run-in (Part I: Cohorts 1.1. and 1.2) and two expansion parts (Parts II and III). Part II will start once all participants in Cohort 1.1 have completed the observation period. Part III will start once all participants in Cohorts 1.1 and 1.2 have completed the observation period.

Conditions

Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with adverse events

  Baseline to end of study (approximately 24 months)

Secondary Outcomes (8)

• Objective Response Rate (ORR)

  Time from first occurrence of a documented objective response until the time of documented disease progression or death from any cause during treatment (whichever occurs first) until the end of study (approximately 24 months)

• Complete Response Rate (CRR)

  Baseline to end of study (approximately 24 months)

• Disease Control Rate (DCR)

  Baseline to end of study (approximately 24 months)

• Duration of Response

  Time from first occurrence of a documented objective response until the time of documented disease progression or death from any cause during treatment (whichever occurs first) until the end of study (approximately 24 months)

• Progression Free Survival (PFS)

  Time from study treatment initiation to the first occurrence of documented disease progression (based on Investigator's assessment) or death from any cause during treatment (whichever occurs first) until the end of study (approximately 24 months)

Study Arms (3)

Part I Safety Run in: RO6874281 + Pembrolizumab

EXPERIMENTAL

Cohort 1.1 (CPI naive and experienced melanoma participants): Participants will receive RO6874281 in combination with Pembrolizumab every 3 weeks (Q3W) and will be observed for 2 cycles (ie: 6 weeks) in order to confirm the safety of the proposed dose and schedule that will be used in Part II of this study. Cohort 1.2 (CPI experienced melanoma participants only): Participants will receive RO6874281 in combination with Pembrolizumab via an induction and maintenance schedule for RO6874281: QW three times (D1, D8, D15) followed by Q3W dosing (D22 and subsequent). Pembrolizumab is to be administered Q3W, starting on Day 1. Participants will be observed for 2 pembrolizumab cycles (ie: 6 weeks) in order to confirm the safety of the proposed dose and schedule that will be used in Part III of this study.

Drug: RO6874281; Drug: Pembrolizumab

Part II Expansion: RO6874281 + Pembrolizumab

EXPERIMENTAL

Part II will start once all participants in Part I Cohort 1.1 have completed the observation period. Approximately 34 participants will receive RO6874281 in combination with Pembrolizumab every 3 weeks (Q3W) and will be observed for 2 cycles (ie: 6 weeks).

Drug: RO6874281; Drug: Pembrolizumab

Part III Expansion: RO6874281 + Pembrolizumab

EXPERIMENTAL

Part III will start once all participants in Part I Cohorts 1.1 and 1.2 have completed the observation period. Approximately 80 participants will be randomised to receive RO6874281 in combination with Pembrolizumab in either a Q3W or QW/Q3W schedule.

Drug: RO6874281; Drug: Pembrolizumab

Interventions

RO6874281 DRUG

Part I Safety Run in: Cohort 1.1: RO6874281 will be administered by intravenous (IV) infusion; 10 mg (Q3W) every 3 weeks and will be observed over 2 administration cycles (i.e. 6 weeks) in order to confirm the safety of the proposed dose and schedule that will be used in Part II of this study. Cohort 1.2: RO6874281 will be administered by IV infusion via an induction and maintenance phase; 10 mg (QW) every week for 3 weeks followed by 10 mg (Q3W) every 3 weeks and will be observed over 2 administration cycles (6 weeks) to confirm safety of the proposed dose and schedule to be used in Part III of this study. Part II Expansion: RO6874281 will be administered by IV infusion; 10 mg (Q3W) every 3 weeks (or lower dose level depending on Part I Cohort 1.1 outcome). Part III Expansion: RO6874281 will be administered by IV infusion; 10 mg (QW) every week or 10mg (Q3W) every 3 weeks (or lower dose level depending on Part I Cohorts 1.1 and 1.2 outcomes) in either a Q3W or QW/Q3W schedule.

Also known as: simlukafusp alfa

Part I Safety Run in: RO6874281 + Pembrolizumab; Part II Expansion: RO6874281 + Pembrolizumab; Part III Expansion: RO6874281 + Pembrolizumab

Pembrolizumab DRUG

Part I Safety Run in (Cohorts 1.1 and 1.2): Pembrolizumab will be administered by IV; 200 mg Q3W and will be observed over 2 administration cycles (i.e. 6 weeks). Part II Expansion: Pembrolizumab will be administered by IV; 200 mg Q3W (or lower dose level depending on Part I Cohort 1.1 outcome) Part III Expansion: Pembrolizumab will be administered by IV; 200 mg Q3W (or lower dose level depending on Part I Cohorts 1.1 and 1.2 outcomes)

Part I Safety Run in: RO6874281 + Pembrolizumab; Part II Expansion: RO6874281 + Pembrolizumab; Part III Expansion: RO6874281 + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed unresectable stage III or stage IV cutaneous or mucosal melanoma (AJCC v8.0).
• Participants need to have known BRAF status.
• CPI naïve melanoma population: Participants with unresectable stage III or stage IV cutaneous or mucosal melanoma who have not received prior treatment for advanced disease. BRAF mutation-positive patients are eligible without prior treatment or after failure of BRAF directed inhibitor therapy.
• CPI experienced melanoma population: Participants with unresectable stage III or stage IV cutaneous melanoma. Participants must have progressed during or after treatment with anti PD-1 antibody therapy, either as monotherapy or in combination with other agent(s).
• Participants should have adequate cardiovascular, hematological, liver, and renal function.
• Participants with unilateral pleural effusion are eligible if they fulfill both of the following: NYHA Class 1; Forced expiratory volume 1 (FEV1) \>70% and forced vital capacity (FVC) \>70% of predicted value; participants with lung metastases should present with DLCO \>60% of predicted value.

You may not qualify if:

• Medical Conditions
• Rapid disease progression or suspected hyperprogression (as determined by the Investigator) or threat to vital organs or critical anatomical sites requiring urgent alternative medical intervention.
• Known active CNS metastases and/or carcinomatous meningitis/leptomeningeal disease:
• Participants with previously treated brain metastases may participate.
• History of treated asymptomatic CNS metastases.
• An active second malignancy (exceptions are non-melanoma skin cancer, cervical carcinoma in situ, or prostate carcinoma that is in remission under androgen deprivation therapy for ≥ 2 years, or participants who have a history of malignancy and have been treated with curative intent and the participant is expected to be cured as per Investigator's assessment).
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, and known autoimmune diseases or other disease with ongoing fibrosis (such as scleroderma, pulmonary fibrosis. and emphysema).
• Episode of significant cardiovascular/cerebrovascular acute disease within 6 months before study treatment administration.
• Active or uncontrolled infections, including latent tuberculosis.
• Known HIV infection.
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Severe infection within 4 weeks before study treatment administration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• History of chronic liver disease or evidence of hepatic cirrhosis.
• Dementia or altered mental status that would prohibit informed consent.
• History of autoimmune disease.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (23)

Yale University

New Haven, Connecticut, 06510, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Melanoma Institute Australia

North Sydney, New South Wales, 2060, Australia

Location

Peter Maccallum Cancer Institute; Clinical Trial Unit

Melbourne, Victoria, 3000, Australia

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Hopital Claude Huriez; Sce Dermatologie

Lille, 59037, France

Location

Hôpital de la Timone; Dermatologie

Marseille, 13005, France

Location

Centre Eugene Marquis; Service d'oncologie

Rennes, 35042, France

Location

Institut Gustave Roussy; Dermatologie

Villejuif, 94805, France

Location

Main Military Clinical Hospital named after N.N. Burdenko

Moscow, Moscow Oblast, 105229, Russia

Location

Russian Oncology Research Center n.a. N.N. Blokhin

Moscow, 115478, Russia

Location

P.A. Gertsen Cancer Research Inst. ; Chemotherapy Dept

Moscow, 125284, Russia

Location

FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"

Saint Petersburg, Russia

Location

Hospital Universitari Vall d'Hebron; Oncology

Barcelona, BARCELONA, 08035, Spain

Location

Hospital Clínic i Provincial; Servicio de Oncología

Barcelona, BARCELONA, 08036, Spain

Location

Clinica Universidad de Navarra Madrid; Servicio de Oncología

Madrid, Madrid, 28027, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, Madrid, 28034, Spain

Location

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, 31008, Spain

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 14, 2019
• Study Start: June 24, 2019
• Primary Completion: July 14, 2022
• Study Completion: July 14, 2022
• Last Updated: October 3, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); CA (2); ES (5); AU (2); RU (4); US (4); BE (2)