Study Evaluating the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Therapeutic Activity of Selicrelumab (RO7009789) With Vanucizumab or Bevacizumab in Participants With Metastatic Solid Tumors

NCT ID: NCT02665416

Last Updated: 2020-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-25
• Study Completion Date: 2019-10-30

Brief Summary

This open-label, two-part study is designed to assess the safety, PK, PD, and therapeutic activity of Selicrelumab in combination with vanucizumab or bevacizumab in participants with metastatic solid tumors not amenable to standard treatment. Part I (dose escalation) is designed to establish the maximum tolerated dose (MTD) of Selicrelumab in this combination. Part II (expansion) is intended to characterize the safety and tolerability of Selicrelumab in combination with bevacizumab among indication-specific cohorts and to confirm the recommended dose.

Conditions

Advanced/Metastatic Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part I: Selicrelumab, Vanucizumab/Bevacizumab

Participants will receive a fixed dose of vanucizumab, 2 grams via IV infusion on Days 1 and 15 of every 28-day cycle. Selicrelumab will be given SC in ascending dose levels on Day 2 of Cycles 1 to 4 and every third cycle thereafter. Treatment will continue as long as the participant experiences clinical benefit or until unacceptable toxicity, withdrawal of consent, or the end of Part I of the study (expected 24 months). Due to the discontinuation of Vanucizumab development, Participants ongoing in Part I will switch from Vanucizumab to Bevacizumab. All the dose escalation has been performed using Vanucizumab.

Group Type: EXPERIMENTAL

Selicrelumab

Intervention Type: DRUG

Selicrelumab will be provided as concentrate for solution to be administered via SC injection

Vanucizumab

Intervention Type: DRUG

Vanucizumab will be provided as solution to be administered via IV infusion.

Part II: Selicrelumab, Bevacizumab

Bevacizumab will be administered via IV infusion on days 1 and 15 of every 28-day cycle. Selicrelumab will be given SC after the Bevacizumab infusion at the dose determined in the Part I of the study on Day 2 of Cycles 1 to 4 and every third cycle thereafter. Treatment will continue as long as the participant experiences clinical benefit or until unacceptable toxicity, withdrawal of consent, or the end of Part II of the study (expected 18 months).

Group Type: EXPERIMENTAL

Selicrelumab

Intervention Type: DRUG

Selicrelumab will be provided as concentrate for solution to be administered via SC injection

Bevacizumab

Intervention Type: DRUG

Bevacizumab will be administered via IV infusion.

Interventions

Selicrelumab

Selicrelumab will be provided as concentrate for solution to be administered via SC injection

Intervention Type: DRUG

Vanucizumab

Vanucizumab will be provided as solution to be administered via IV infusion.

Intervention Type: DRUG

Bevacizumab

Bevacizumab will be administered via IV infusion.

Intervention Type: DRUG

Other Intervention Names

RO7009789

Eligibility Criteria

Inclusion Criteria

• Part I: Histologically confirmed advanced/metastatic solid tumor (except prostate cancer and squamous non-small cell lung cancer [NSCLC])
• Part II: Histologically confirmed advanced/metastatic platinum-resistant ovarian carcinoma (aPROC), head and neck squamous cell carcinoma (HNSCC), or non-squamous NSCLC previously treated with anti-PD-L1/PD-1 inhibitor alone or in combination (e.g. atezolizumab, nivolumab, pembrolizumab, durvalumab, avelumab)
• Checkpoint inhibitor (CPI)- experienced patients must have experienced documented disease progression on or after PD-L1/PD-1 inhibitor therapy
• In CPI-experienced patients, the PD-L1/PD-1 inhibitor must have been part of the most recent systemic anticancer therapy administered prior to study enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy >/= 16 weeks
• Adequate hematologic, renal, hepatic, and cardiovascular function
• Measurable disease per Response Evaluation Criteria in Solid Tumors, v 1.1 (RECIST v1.1)
• Tumors must be acceptable for biopsy. Participants in Part II may be enrolled without a biopsy if the collection is not clinically feasible.
• Agreement to use adequate contraceptive measures among men or among women of childbearing potential

Exclusion Criteria

• Prostate cancer or squamous NSCLC
• Recent systemic anti-cancer treatment
• Prior treatment with anti-programmed death (PD) 1 or anti-programmed death ligand (PD-L) 1 therapeutic antibody, vanucizumab, or compounds targeting cluster of differentiation (CD) 40 less than 4 weeks or 5xt1/2 (whichever is shorter) prior to enrollment
• Part II: Treatment targeting vascular endothelial growth factor (VEGF) or receptor within 12 months prior to enrollment
• Systemic immunosuppressive medication within 2 weeks prior to day 1 of cycle 1
• Chronic daily treatment with non-steroidal anti-inflammatory drugs
• Unacceptable/unresolved toxicity from prior anti-cancer therapy
• Patients who have had a surgical procedure or significant traumatic injury within 28 days prior to initiation of study treatment, or a core biopsy or other minor surgical procedure within 7 days prior to initiation of study treatment
• Bisphosphonate therapy for symptomatic hypercalcemia
• Significant vascular disease
• History of hypertensive crisis or hypertensive encephalopathy
• Current or recent use of aspirin (>325 mg/day) or clopidogrel (>75 mg/day)
• History of vein thrombosis/thromboembolism, or use of anticoagulants within 7 days prior to study drug
• Primary tumor in place in participants with colorectal cancer, or evidence of bowel involvement (metastasis, direct tumor invasion) in participants with other non-gastrointestinal cancer
• Significant cardiovascular or cerebrovascular disease within 6 months prior to D1 of C1
• History of fistula, bowel obstruction, perforation, or abscess
• Prior radiotherapy to pelvis or abdomen, recto-sigmoid involvement, or bowel involvement among participants with aPROC
• Severe non-healing wound, active ulcer or untreated bone fracture
• Pregnant or lactating women
• History of autoimmune disease
• Human immunodeficiency virus (HIV) or hepatitis B or C
• Severe infection or receipt of a live/attenuated vaccine within 4 weeks prior to D1 of C1
• Other significant malignancies within 3 years prior to D1 of C1
• Allergy/hypersensitivity to study drug
• Prior allogeneic bone marrow or solid organ transplant
• Other conditions/findings that may contraindicate use of study drug
• Major surgery within 4 weeks prior to study drug
• Known clinically significant liver disease
• History of hemoptysis or bleeding diathesis, or known coagulopathies
• Known symptomatic or untreated central nervous system (CNS) malignancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Cedars Sinai Medical Center

Los Angeles, California, United States

Univ of CO Health Science Ctr

Denver, Colorado, United States

Yale Cancer Center; Medical Oncology

New Haven, Connecticut, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Cliniques Universitaires St-Luc

Brussels, , Belgium

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, Canada

Rigshospitalet; Onkologisk Klinik

København Ø, , Denmark

Irccs Ospedale San Raffaele;Oncologia Medica

Milan, Lombardy, Italy

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Erasmus Medisch Centrum

Rotterdam, , Netherlands

ICO L'Hospitalet; Servicio de oncologia medica

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital del Mar; Servicio de Oncologia

Barcelona, , Spain

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

Madrid, , Spain

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, , Spain

Countries

United States; Belgium; Canada; Denmark; Italy; Netherlands; Spain

Other Identifiers

2015-003480-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RG7876

Identifier Type: OTHER

Identifier Source: secondary_id

BP29889

Identifier Type: -

Identifier Source: org_study_id