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:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase IB Study To Evaluate Safety And Therapeutic Activity Of RO6874281, An Immunocytokine, Consisting Of Interleukin-2 Variant Targeting Fibroblast Activation Protein-Α, In Combination With Pembrolizumab (Anti-Pd-1), In Participants With Previously Untreated Advanced And/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 Previously Untreated Advanced And/Or Metastatic Melanoma

Clinical Trial IDs

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

Conditions

  • Metastatic Melanoma

Interventions

DrugSynonymsArms
RO6874281Part 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 2 parts: a safety run-in (Part I) and an expansion (Part II). Part II will start once all participants in Part I have completed the observation period.

Trial Arms

NameTypeDescriptionInterventions
Part I Safety Run in: RO6874281 + PembrolizumabExperimentalParticipants will receive RO6874281 in combination with Pembrolizumab every 3 weeks 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.
  • RO6874281
  • Pembrolizumab
Part II Expansion: RO6874281 + PembrolizumabExperimentalPart II will start once all participants in Part I have completed the observation period. Participants will receive RO6874281 in combination with Pembrolizumab every 3 weeks and will be observed for 2 cycles (ie: 6 weeks).
  • RO6874281
  • Pembrolizumab

Eligibility Criteria

        Inclusion criteria:

          -  Participants with unresectable locally advanced (Stages IIIC and IIID) and metastatic
             (recurrent or de novo Stage IV) invasive cutaneous or mucosal melanoma that is
             measurable and who have not received prior treatment for advanced disease.
             Participants need to have known BRAF status. BRAF mutation-positive patients are
             eligible without prior treatment or after failure of BRAF directed inhibitor therapy

          -  Measurable disease, as defined by Response evaluation criteria in solid tumors version
             1.1 (RECIST v1.1)

          -  Eastern Cooperative Oncology Group Performance Status 0 or 1 or Karnofsky Performance
             Score >= 70

          -  Life expectancy of >= 12 weeks

          -  Confirmed at least one tumor lesion with location accessible to safely biopsy per
             clinical judgment of the treating physician and the participant's consented
             willingness to undergo baseline tumor biopsies for Pharmacodynamic biomarker analysis

          -  Consent to provide an archival tumor tissue sample

          -  Adequate cardiovascular, hematological function, liver, renal function

          -  Adverse events related to any previous radiotherapy, chemotherapy, or surgical
             procedure must have resolved to Grade <= 1, except alopecia and Grade 2 peripheral
             neuropathy

          -  Participants with unilateral pleural effusion are eligible

          -  Female participants: A female participant is eligible to participate if she is not
             pregnant, not breastfeeding, not a woman of childbearing potential or agrees to remain
             abstinent or use contraceptive methods that result in a failure rate of <= 1% per year
             during the treatment period and for at least 4 months after the last dose of study
             drug for RO6874281 and for at least 4 months after the last dose of pembrolizumab.
             Have a negative pregnancy test within the 7 days before the first study treatment
             administration.

          -  Male participants: Remain abstinent or use contraceptive measures such as a condom
             plus an additional contraceptive method that together result in a failure rate of <=
             1% per year, with partners who are women of childbearing potential during the
             treatment period and for at least 2 months after the last dose of RO6874281. Refrain
             from donating sperm.

          -  Participants with Gilbert's syndrome will be eligible for the study. The diagnosis of
             Gilbert's syndrome is suspected in people who have persistent, slightly elevated
             levels of unconjugated bilirubin without any other apparent cause

        Exclusion Criteria:

          -  Rapid disease progression or threat to vital organs or critical anatomical sites
             requiring urgent alternative medical intervention

          -  Symptomatic or untreated central nervous system (CNS) metastases

          -  History of treated asymptomatic Central Nervous System (CNS) metastases

          -  Spinal cord compression not definitively treated with surgery and/or radiation or
             previously diagnosed and treated spinal cord compression without evidence that disease
             has been clinically stable for >= 2 weeks before enrollment

          -  Leptomeningeal disease

          -  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,
             including diabetes mellitus, history of relevant pulmonary disorders, and known
             autoimmune diseases or other disease with ongoing fibrosis

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

          -  Active or uncontrolled infections, including latent tuberculosis

          -  Known human immunodeficiency virus (HIV) infection

          -  Active hepatitis B virus or hepatitis C virus 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, active or suspicion of autoimmune disease (participants with autoimmune
             hypothyroidism and/or hypopituitarism may be eligible after consultation with
             Sponsor), idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or
             evidence of active pneumonitis on screening chest computed tomography scan and
             radiation pneumonitis in the radiation field is permitted

          -  Bilateral pleural effusion confirmed by x ray

          -  Severe dyspnea at rest or requiring supplementary oxygen therapy

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding that give reasonable suspicion of a disease or condition that would
             contraindicate the use of an investigational drug

          -  Concurrent therapy with any other investigational drug

          -  Immunomodulating agents

          -  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. Acute and/or low dose systemic
             immunosuppressive medications may be acceptable after consultation with the Sponsor

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

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

          -  Patients with previous treatment containing a checkpoint inhibitor (CPI) are not
             allowed in this study. Eligibility of participants who had received CPI as adjuvant
             treatment for previous localized disease need to be discussed and agreed upon with the
             Sponsor before screening

        Other Exclusions

          -  Major surgery or significant traumatic injury < 28 days before study treatment
             administration or anticipation of the need for major surgery during study treatment

          -  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

          -  Participant eligibility for treatment with Pembrolizumab should be verified against
             the pembrolizumab labeling documents
      
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

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