Clinical Trials /

A Study To Evaluate Safety And Therapeutic Activity Of RO6874281 In Combination With Pembrolizumab, In Participants With Advanced Or Metastatic Melanoma

NCT03875079

Description:

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.

Related Conditions:
  • Cutaneous Melanoma
  • Mucosal Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study To Evaluate Safety And Therapeutic Activity Of RO6874281 In Combination With Pembrolizumab, In Participants With Advanced Or Metastatic Melanoma
  • Official Title: An Open-Label, Multicenter, Phase Ib Study To Evaluate Safety And Therapeutic Activity Of RO6874281, An Immunocytokine, Consisting Of Interleukin-2 Variant (IL-2v) Targeting Fibroblast Activation Protein-Α (FAP), In Combination With Pembrolizumab (Anti-PD-1), In Participants With Advanced Or Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: BP41054
  • SECONDARY ID: 2018-003872-11
  • NCT ID: NCT03875079

Conditions

  • Metastatic Melanoma

Interventions

DrugSynonymsArms
RO6874281simlukafusp alfaPart I Safety Run in: RO6874281 + Pembrolizumab
PembrolizumabPart I Safety Run in: RO6874281 + Pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part I Safety Run in: RO6874281 + PembrolizumabExperimentalCohort 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.
  • RO6874281
  • Pembrolizumab
Part II Expansion: RO6874281 + PembrolizumabExperimentalPart 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).
  • RO6874281
  • Pembrolizumab
Part III Expansion: RO6874281 + PembrolizumabExperimentalPart 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.
  • RO6874281
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically confirmed unresectable stage III or stage IV cutaneous or mucosal
             melanoma (AJCC v8.0).

          2. Participants need to have known BRAF status.

          3. 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.

          4. 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).

          5. Participants should have adequate cardiovascular, hematological, liver, and renal
             function.

          6. 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.

        Exclusion criteria:

        Medical Conditions

          1. 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.

          2. Known active CNS metastases and/or carcinomatous meningitis/leptomeningeal disease:

             Participants with previously treated brain metastases may participate.

          3. History of treated asymptomatic CNS metastases.

          4. 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).

          5. 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).

          6. Episode of significant cardiovascular/cerebrovascular acute disease within 6 months
             before study treatment administration.

          7. Active or uncontrolled infections, including latent tuberculosis.

          8. Known HIV infection.

          9. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

         10. Severe infection within 4 weeks before study treatment administration, including, but
             not limited to, hospitalization for complications of infection, bacteremia, or severe
             pneumonia.

         11. History of chronic liver disease or evidence of hepatic cirrhosis.

         12. Dementia or altered mental status that would prohibit informed consent.

         13. History of autoimmune disease.

         14. Adverse events related to any previous radiotherapy, chemotherapy, targeted therapy,
             CPI therapy or surgical procedure that have not resolved to Grade =< 1, except
             alopecia (any grade) and Grade 2 peripheral neuropathy.

         15. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
             tomography (CT) scan.

         16. Bilateral pleural effusion.

         17. Severe dyspnea at rest or requiring supplementary oxygen therapy.

         18. Concurrent therapy with any other investigational drug (defined as a treatment for
             which there is currently no regulatory authority approved indication).

         19. Immunomodulating agents: Last dose with any of the following agents, for example,
             etanercept, infliximab, tacrolimus, cyclosporine, mycophenolic acid, alefacept, or
             efalizumab (or similar agents) < 28 days before study treatment administration.
             Regular immunosuppressive therapy (i.e., for organ transplantation, chronic
             rheumatologic disease)

         20. Treatment with systemic immunosuppressive medications including, but not limited to
             prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF
             agents within 2 weeks prior to Cycle 1 Day 1.

         21. Radiotherapy within the last 4 weeks before start of study treatment administration,
             with the exception of limited field palliative radiotherapy.

         22. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1.

         23. Major surgery or significant traumatic injury < 28 days before study treatment
             administration (excluding fine needle biopsies) or anticipation of the need for major
             surgery during study treatment.

         24. Known hypersensitivity to any of the components of the RO6874281 drug product or
             pembrolizumab drug product, including but not limited to hypersensitivity to Chinese
             Hamster Ovary cell products or other recombinant human or humanized antibodies.

         25. No prior cytotoxic therapy for unresectable stage III or stage IV disease is
             permitted.

         26. Toxicity from prior anti-PD-1 antibody therapy (including adjuvant treatment).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of participants with adverse events
Time Frame:Baseline to end of study (approximately 24 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame: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)
Safety Issue:
Description:
Measure:Complete Response Rate (CRR)
Time Frame:Baseline to end of study (approximately 24 months)
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:Baseline to end of study (approximately 24 months)
Safety Issue:
Description:
Measure:Duration of Response
Time Frame: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)
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame: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)
Safety Issue:
Description:
Measure:Baseline PD-L1
Time Frame:Baseline to end of study (approximately 24 months)
Safety Issue:
Description:
Measure:Fibroblast Activation Protein-a (FAP)
Time Frame:Baseline to end of study (approximately 24 months)
Safety Issue:
Description:
Measure:Change from baseline in density (cell/mm2) of immune cells including CD8+, FOXP3, and PD-L1
Time Frame:Baseline to end of study (approximately 24 months)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

November 12, 2020