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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03875079




Registration number
NCT03875079
Ethics application status
Date submitted
13/03/2019
Date registered
14/03/2019

Titles & IDs
Public title
A Study to Evaluate Safety and Therapeutic Activity of RO6874281 in Combination with Pembrolizumab, in Participants with Advanced or Metastatic Melanoma
Scientific 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-? (FAP), in Combination with Pembrolizumab (Anti-PD-1), in Participants with Advanced or Metastatic Melanoma
Secondary ID [1] 0 0
2018-003872-11
Secondary ID [2] 0 0
BP41054
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RO6874281
Treatment: Drugs - Pembrolizumab

Experimental: Part I Safety Run in: RO6874281 + Pembrolizumab - Cohort 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.

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

Experimental: Part III Expansion: RO6874281 + Pembrolizumab - Part 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.


Treatment: Drugs: RO6874281
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.

Treatment: Drugs: Pembrolizumab
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)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of participants with adverse events
Timepoint [1] 0 0
Baseline to end of study (approximately 24 months)
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Complete Response Rate (CRR)
Timepoint [2] 0 0
Baseline to end of study (approximately 24 months)
Secondary outcome [3] 0 0
Disease Control Rate (DCR)
Timepoint [3] 0 0
Baseline to end of study (approximately 24 months)
Secondary outcome [4] 0 0
Duration of Response
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Progression Free Survival (PFS)
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Baseline PD-L1
Timepoint [6] 0 0
Baseline to end of study (approximately 24 months)
Secondary outcome [7] 0 0
Fibroblast Activation Protein-a (FAP)
Timepoint [7] 0 0
Baseline to end of study (approximately 24 months)
Secondary outcome [8] 0 0
Change from baseline in density (cell/mm2) of immune cells including CD8+, FOXP3, and PD-L1
Timepoint [8] 0 0
Baseline to end of study (approximately 24 months)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/07/2022
Sample size
Target
Accrual to date
Final
83
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [2] 0 0
Peter Maccallum Cancer Institute; Clinical Trial Unit - Melbourne
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Iowa
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
Belgium
State/province [4] 0 0
Edegem
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
France
State/province [8] 0 0
Lille
Country [9] 0 0
France
State/province [9] 0 0
Marseille
Country [10] 0 0
France
State/province [10] 0 0
Rennes
Country [11] 0 0
France
State/province [11] 0 0
Villejuif
Country [12] 0 0
Russian Federation
State/province [12] 0 0
Moskovskaja Oblast
Country [13] 0 0
Russian Federation
State/province [13] 0 0
Moscow
Country [14] 0 0
Russian Federation
State/province [14] 0 0
Saint-Petersburg
Country [15] 0 0
Spain
State/province [15] 0 0
Navarra
Country [16] 0 0
Spain
State/province [16] 0 0
Barcelona
Country [17] 0 0
Spain
State/province [17] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03875079