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

NCT02665416 | Completed Phase 1 FDA Drug

• 3 other identifiers: BP298892015-003480-11RG7876
• Study Type: interventional
• Target: 94
• Locations: 7 countries
• Sites: 16

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

Outcome Measures

Primary Outcomes (9)

• Percentage of Participants With Dose-Limiting Toxicities (DLTs)

  From Day (D) 1 until D28 of Cycle (C)1 (cycle length=28 days)

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• MTD of Selicrelumab in Combination With Vanucizumab

  From D1 until D28 of C1 (cycle length=28 days)

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Recommended Phase II Dose of Selicrelumab in Combination With Vanucizumab

  From D1 until D28 of C1 (cycle length=28 days)

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Percentage of Participants With Adverse Events (AEs)

  From D1 of C1 until treatment discontinuation and approximately 45 days after last dose (cycle length=28 days)

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Part II: Clinical Activity of SC Selicrelumab in Combination with Bevacizumab as Assessed by Response Evaluation in Solid Tumors, Version 1.1 (RECIST v1.1)

  From D1 of C1 through safety follow up visit (45 days post final dose; Cycle = 28 days)

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Part II: Percentage of Participants With Best Overall Response per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria

  Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Part II: Duration of Objective Response per RECIST v1.1 Criteria

  Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)

  TBaseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Part II: Percentage of Participants With Disease Control per RECIST v1.1 Criteria

  Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Part II: Progression-free Survival (PFS) per RECIST v1.1 Criteria

  Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

Secondary Outcomes (31)

• Percentage of Participants With Anti-Drug Antibodies (ADAs) to Selicrelumab

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Percentage of Participants with ADAs to Vanucizumab

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Area Under the Concentration-Time Curve From Time 0 to Last Measureable Concentration (AUClast) of Selicrelumab Following Subcutaneous (SC) Administration

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Selicrelumab Following SC Administration

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

• Maximum Concentration (Cmax) of Selicrelumab Following SC Administration

  Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)

Study Arms (2)

Part I: Selicrelumab, Vanucizumab/Bevacizumab

EXPERIMENTAL

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.

Drug: Selicrelumab; Drug: Vanucizumab

Part II: Selicrelumab, Bevacizumab

EXPERIMENTAL

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).

Drug: Selicrelumab; Drug: Bevacizumab

Interventions

Selicrelumab DRUG

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

Also known as: RO7009789

Part I: Selicrelumab, Vanucizumab/Bevacizumab; Part II: Selicrelumab, Bevacizumab

Vanucizumab DRUG

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

Part I: Selicrelumab, Vanucizumab/Bevacizumab

Bevacizumab DRUG

Bevacizumab will be administered via IV infusion.

Part II: Selicrelumab, Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (16)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Univ of CO Health Science Ctr

Denver, Colorado, 80262, United States

Location

Yale Cancer Center; Medical Oncology

New Haven, Connecticut, 06520, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9, Canada

Location

Rigshospitalet; Onkologisk Klinik

København Ø, 2100, Denmark

Location

Irccs Ospedale San Raffaele;Oncologia Medica

Milan, Lombardy, 20132, Italy

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 GD, Netherlands

Location

ICO L'Hospitalet; Servicio de oncologia medica

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital del Mar; Servicio de Oncologia

Barcelona, 08003, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, 46010, Spain

Location

MeSH Terms

Interventions

selicrelumab; vanucizumab; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: January 27, 2016
• Study Start: January 25, 2016
• Primary Completion: October 30, 2019
• Study Completion: October 30, 2019
• Last Updated: April 7, 2020

Record last verified: 2020-04

Locations

US (5); BE (1); ES (5); CA (1); DK (1); IT (1); NL (2)