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History of Changes for Study: NCT03875079
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
Latest version (submitted June 13, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 13, 2019 None (earliest Version on record)
2 April 15, 2019 Recruitment Status, Study Status and Contacts/Locations
3 May 21, 2019 Study Status and Contacts/Locations
4 August 28, 2019 Study Status and Contacts/Locations
5 November 20, 2019 Contacts/Locations, Arms and Interventions, Study Design, Study Status, Study Identification, IPDSharing, Eligibility and Study Description
6 December 19, 2019 Study Status and Contacts/Locations
7 January 14, 2020 Study Status and Contacts/Locations
8 February 13, 2020 Study Status and Contacts/Locations
9 March 19, 2020 Study Status and Contacts/Locations
10 April 14, 2020 Study Status
11 April 23, 2020 Arms and Interventions and Study Status
12 June 16, 2020 Study Status and Contacts/Locations
13 July 13, 2020 Contacts/Locations and Study Status
14 August 10, 2020 Study Status and Contacts/Locations
15 September 7, 2020 Study Status and Contacts/Locations
16 October 8, 2020 Study Status and Contacts/Locations
17 November 10, 2020 Study Status and Contacts/Locations
18 December 9, 2020 Study Status and Contacts/Locations
19 January 4, 2021 Study Status and Contacts/Locations
20 February 2, 2021 Study Status and Contacts/Locations
21 March 3, 2021 Recruitment Status, Study Status, Contacts/Locations and Study Design
22 April 1, 2021 Study Status
23 June 30, 2021 Study Status and Contacts/Locations
24 September 30, 2021 Study Status
25 December 20, 2021 Study Status
26 March 15, 2022 Study Status
27 June 13, 2022 Study Status and Contacts/Locations
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Study NCT03875079
Submitted Date:  March 13, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: BP41054
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
Secondary IDs: 2018-003872-11 [EudraCT Number]
Open or close this module Study Status
Record Verification: March 2019
Overall Status: Not yet recruiting
Study Start: April 10, 2019
Primary Completion: February 2, 2020 [Anticipated]
Study Completion: December 1, 2020 [Anticipated]
First Submitted: March 13, 2019
First Submitted that
Met QC Criteria:
March 13, 2019
First Posted: March 14, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
March 13, 2019
Last Update Posted: March 14, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Hoffmann-La Roche
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
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 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.
Detailed Description:
Open or close this module Conditions
Conditions: Metastatic Melanoma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 40 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Part I Safety Run in: RO6874281 + Pembrolizumab
Participants 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.
Drug: RO6874281

Part I Safety Run in: 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.

Part II Expansion: RO6874281 will be administered by intravenous (IV) infusion; 10 mg (Q3W) every 3 weeks (or lower dose level depending on Part I outcome)

Drug: Pembrolizumab

Part I Safety Run in: 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 outcome)

Experimental: Part II Expansion: RO6874281 + Pembrolizumab
Part 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).
Drug: RO6874281

Part I Safety Run in: 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.

Part II Expansion: RO6874281 will be administered by intravenous (IV) infusion; 10 mg (Q3W) every 3 weeks (or lower dose level depending on Part I outcome)

Drug: Pembrolizumab

Part I Safety Run in: 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 outcome)

Open or close this module Outcome Measures
Primary Outcome Measures:
1. Percentage of participants with adverse events
[ Time Frame: Baseline to end of study (approximately 24 months) ]

Secondary Outcome Measures:
1. 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) ]

2. Complete Response Rate (CRR)
[ Time Frame: Baseline to end of study (approximately 24 months) ]

3. Disease Control Rate (DCR)
[ Time Frame: Baseline to end of study (approximately 24 months) ]

4. 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) ]

5. 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) ]

6. Baseline PD-L1
[ Time Frame: Baseline to end of study (approximately 24 months) ]

7. Fibroblast Activation Protein-a (FAP)
[ Time Frame: Baseline to end of study (approximately 24 months) ]

8. 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) ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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
Open or close this module Contacts/Locations
Central Contact Person: Reference Study ID Number: BP41054 www.roche.com/about_roche/roche_worldwide.htm
Telephone: 888-662-6728 (U.S. and Canada)
Email: global-roche-genentech-trials@gene.com
Study Officials: Clinical Trials
Study Director
Hoffmann-La Roche
Locations: Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Spain, Navarra
Clinica Universitaria de Navarra; Servicio de Oncologia
Pamplona, Navarra, Spain, 31008
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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