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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

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ClinicalTrials.gov Identifier: NCT03875079
Recruitment Status : Recruiting
First Posted : March 14, 2019
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Drug: RO6874281 Drug: Pembrolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : May 24, 2019
Estimated Primary Completion Date : February 2, 2020
Estimated Study Completion Date : December 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
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)





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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03875079


Contacts
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Contact: Reference Study ID Number: BP41054 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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Canada, Ontario
Princess Margaret Cancer Centre Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital Not yet recruiting
Montreal, Quebec, Canada, H3T 1E2
France
Hôpital de la Timone; Dermatologie Not yet recruiting
Marseille, France, 13005
Centre Eugene Marquis; Service d'oncologie Not yet recruiting
Rennes, France, 35042
Institut Gustave Roussy; Dermatologie Not yet recruiting
Villejuif, France, 94805
Spain
Clinica Universitaria de Navarra; Servicio de Oncologia Recruiting
Pamplona, Navarra, Spain, 31008
Hospital Universitari Vall d'Hebron; Oncology Recruiting
Barcelona, Spain, 08035
Hospital Clínic i Provincial; Servicio de Oncología Not yet recruiting
Barcelona, Spain, 08036
Hospital Ramon y Cajal; Servicio de Oncologia Recruiting
Madrid, Spain, 28034
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03875079     History of Changes
Other Study ID Numbers: BP41054
2018-003872-11 ( EudraCT Number )
First Posted: March 14, 2019    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Interleukin-2
Antineoplastic Agents, Immunological
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs