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Metastatic MelanomaPhase 1NCT03875079

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

A Phase 1 study testing RO6874281 and Pembrolizumab in people with Metastatic Melanoma, run by Hoffmann-La Roche at 23 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma
What is being tested?
RO6874281 and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
23 sitesin 7 countries
Study dates
24 Jun 2019to 14 Jul 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
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  • 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.
  • 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.
  • 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.
  • Bilateral pleural effusion.
  • Severe dyspnea at rest or requiring supplementary oxygen therapy.
  • Concurrent therapy with any other investigational drug (defined as a treatment for which there is currently no regulatory authority approved indication).
  • 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)
  • 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.
  • 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.
  • 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.
  • 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.
  • No prior cytotoxic therapy for unresectable stage III or stage IV disease is permitted.
  • Toxicity from prior anti-PD-1 antibody therapy (including adjuvant treatment).

Trial locations and contacts

23 sites in 7 countries.

23 sites in 7 countries

Spain5 sites

  • Hospital Universitari Vall d'Hebron; Oncology

    Barcelona, BARCELONA, 08035

  • Hospital Clínic i Provincial; Servicio de Oncología

    Barcelona, BARCELONA, 08036

  • Clinica Universidad de Navarra Madrid; Servicio de Oncología

    Madrid, Madrid, 28027

  • Hospital Ramon y Cajal; Servicio de Oncologia

    Madrid, Madrid, 28034

  • Clinica Universitaria de Navarra; Servicio de Oncologia

    Pamplona, Navarre, 31008

Other trials in Spain

United States4 sites

  • Beth Israel Deaconess Med Ctr

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Iowa

    Iowa City, Iowa, 52242

  • Yale University

    New Haven, Connecticut, 06510

Other trials in United States

France4 sites

  • Hopital Claude Huriez; Sce Dermatologie

    Lille, 59037

  • Hôpital de la Timone; Dermatologie

    Marseille, 13005

  • Centre Eugene Marquis; Service d'oncologie

    Rennes, 35042

  • Institut Gustave Roussy; Dermatologie

    Villejuif, 94805

Other trials in France

Russia4 sites

  • Main Military Clinical Hospital named after N.N. Burdenko

    Moscow, Moscow Oblast, 105229

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

    Moscow, 115478

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

    Moscow, 125284

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

    Saint Petersburg

Other trials in Russia

Australia2 sites

  • Peter Maccallum Cancer Institute; Clinical Trial Unit

    Melbourne, Victoria, 3000

  • Melanoma Institute Australia

    North Sydney, New South Wales, 2060

Other trials in Australia

Belgium2 sites

  • UZ Antwerpen

    Edegem, 2650

  • UZ Leuven Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Canada2 sites

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 1Z5

Other trials in Canada

About this study

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

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.

Being tested
RO6874281, Pembrolizumab
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RO6874281Drug

    Also called simlukafusp alfa

    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.

  • PembrolizumabDrug

    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)

Study groups in NCT03875079
Study groupRoleWhat they receive
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.
Receives: Drug: RO6874281; Drug: 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).
Receives: Drug: RO6874281; Drug: 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.
Receives: Drug: RO6874281; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of participants with adverse events

    Measured: Baseline to end of study (approximately 24 months)

Secondary outcomes (8)

  1. Objective Response Rate (ORR)

    Measured: 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)

    Measured: Baseline to end of study (approximately 24 months)

  3. Disease Control Rate (DCR)

    Measured: Baseline to end of study (approximately 24 months)

  4. Duration of Response

    Measured: 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)

    Measured: 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

    Measured: Baseline to end of study (approximately 24 months)

  7. Fibroblast Activation Protein-a (FAP)

    Measured: 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

    Measured: Baseline to end of study (approximately 24 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2019
  2. Study start24 Jun 2019
  3. Primary completion14 Jul 2022
  4. Study completion14 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03875079
Sponsor's protocol ID
BP41054
Other IDs
2018-003872-11, 2018
Status last verified
Oct 2024
First submitted
13 Mar 2019
Last updated
3 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RO6874281 and Pembrolizumab in people with Metastatic Melanoma, run by Hoffmann-La Roche at 23 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Spain, United States, France, Russia, Australia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of participants with adverse events (time frame: Baseline to end of study (approximately 24 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03875079.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2024.

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