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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03875079
Registration number
NCT03875079
Ethics application status
Date submitted
13/03/2019
Date registered
14/03/2019
Date last updated
29/03/2023
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
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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
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Secondary ID [1]
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2018-003872-11
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Secondary ID [2]
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BP41054
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Metastatic Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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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)
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of participants with adverse events
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Assessment method [1]
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Timepoint [1]
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Baseline to end of study (approximately 24 months)
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Secondary outcome [1]
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Objective Response Rate (ORR)
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Assessment method [1]
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Timepoint [1]
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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)
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Secondary outcome [2]
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Complete Response Rate (CRR)
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Assessment method [2]
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Timepoint [2]
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Baseline to end of study (approximately 24 months)
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Secondary outcome [3]
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Disease Control Rate (DCR)
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Assessment method [3]
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Timepoint [3]
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Baseline to end of study (approximately 24 months)
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Secondary outcome [4]
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Duration of Response
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Assessment method [4]
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Timepoint [4]
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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)
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Secondary outcome [5]
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Progression Free Survival (PFS)
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Assessment method [5]
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Timepoint [5]
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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)
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Secondary outcome [6]
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Baseline PD-L1
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Assessment method [6]
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Timepoint [6]
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Baseline to end of study (approximately 24 months)
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Secondary outcome [7]
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Fibroblast Activation Protein-a (FAP)
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Assessment method [7]
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Timepoint [7]
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Baseline to end of study (approximately 24 months)
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Secondary outcome [8]
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Change from baseline in density (cell/mm2) of immune cells including CD8+, FOXP3, and PD-L1
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Assessment method [8]
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Timepoint [8]
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Baseline to end of study (approximately 24 months)
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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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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).
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
24/06/2019
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
14/07/2022
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Sample size
Target
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Accrual to date
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Final
83
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Recruitment in Australia
Recruitment state(s)
NSW,VIC
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Recruitment hospital [1]
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Melanoma Institute Australia - North Sydney
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Recruitment hospital [2]
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Peter Maccallum Cancer Institute; Clinical Trial Unit - Melbourne
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Recruitment postcode(s) [1]
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2060 - North Sydney
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Recruitment postcode(s) [2]
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3000 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Connecticut
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United States of America
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State/province [2]
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Iowa
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United States of America
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Massachusetts
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Belgium
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Edegem
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Belgium
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Leuven
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Canada
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Ontario
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Canada
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Quebec
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France
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Lille
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Country [9]
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France
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Marseille
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France
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Rennes
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France
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State/province [11]
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Villejuif
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Country [12]
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Russian Federation
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State/province [12]
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Moskovskaja Oblast
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Russian Federation
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Moscow
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Russian Federation
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State/province [14]
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Saint-Petersburg
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Spain
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Navarra
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Spain
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Barcelona
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Spain
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Madrid
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Hoffmann-La Roche
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Address
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Ethics approval
Ethics application status
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Summary
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 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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03875079
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Address
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Hoffmann-La Roche
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Contact person for public queries
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03875079
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