Study to Evaluate Safety, Pharmacokinetics and Therapeutic Activity of RO6874281 as a Combination Therapy in Participants With Unresectable Advanced and/or Metastatic Renal Cell Carcinoma (RCC)

NCT ID: NCT03063762

Last Updated: 2023-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-20
• Study Completion Date: 2021-06-14

Brief Summary

This is an open-label, multi-center, randomized, Phase 1b, adaptive, clinical study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary therapeutic activity of RO6874281 in combination with atezolizumab with/without bevacizumab in participants with unresectable advanced and/or metastatic RCC. The study will consist of a dose-escalation part and an extension part.

Conditions

Renal Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Escalation Part (Arm A): Atezolizumab, RO6874281

Participants will receive RO6874281 in combination with atezolizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has complete response (CR), treatment may be discontinued and reintroduced if progressive disease (PD), for a maximum duration of 24 months.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Arms A and B Atezolizumab will be administered at a dose of 840 milligrams (mg) prior to RO6874281 administration as an intravenous (IV) infusion on Days 1, 15, 29, and once in 2 weeks from Day 29 onwards. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

Arms C and D Atezolizumab will be administered at a dose of 1200mg as it is a Q3W schedule

RO6874281

Intervention Type: DRUG

Arms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part

Escalation Part (Arm B): Atezolizumab, Bevacizumab, RO6874281

Participants will receive RO6874281 in combination with atezolizumab and bevacizumab until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Arms A and B Atezolizumab will be administered at a dose of 840 milligrams (mg) prior to RO6874281 administration as an intravenous (IV) infusion on Days 1, 15, 29, and once in 2 weeks from Day 29 onwards. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

Arms C and D Atezolizumab will be administered at a dose of 1200mg as it is a Q3W schedule

Bevacizumab

Intervention Type: DRUG

Arms A and B Bevacizumab will be administered at a dose of 10 milligrams per kilogram (mg/kg) after the atezolizumab administration, and prior to RO6874281 administration as an IV infusion on Days 15, 29, and once in 2 weeks from Day 29 onwards.

In Arm D, Bevacizumab will be administered at a dose of 15mg/kg on Day 8 of Cycle 2 and on Day 8 of each consecutive cycle.

RO6874281

Intervention Type: DRUG

Arms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part

Extension Part (Arm A): Atezolizumab, RO6874281

Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months.

Note: no new participants are being enrolled in the arm at this time.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Arms A and B Atezolizumab will be administered at a dose of 840 milligrams (mg) prior to RO6874281 administration as an intravenous (IV) infusion on Days 1, 15, 29, and once in 2 weeks from Day 29 onwards. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

Arms C and D Atezolizumab will be administered at a dose of 1200mg as it is a Q3W schedule

RO6874281

Intervention Type: DRUG

Arms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part

Extension Part (Arm B): Atezolizumab, Bevacizumab, RO6874281

Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab and bevacizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months.

Note: no new participants are being enrolled in the arm at this time.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Arms A and B Atezolizumab will be administered at a dose of 840 milligrams (mg) prior to RO6874281 administration as an intravenous (IV) infusion on Days 1, 15, 29, and once in 2 weeks from Day 29 onwards. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

Arms C and D Atezolizumab will be administered at a dose of 1200mg as it is a Q3W schedule

Bevacizumab

Intervention Type: DRUG

Arms A and B Bevacizumab will be administered at a dose of 10 milligrams per kilogram (mg/kg) after the atezolizumab administration, and prior to RO6874281 administration as an IV infusion on Days 15, 29, and once in 2 weeks from Day 29 onwards.

In Arm D, Bevacizumab will be administered at a dose of 15mg/kg on Day 8 of Cycle 2 and on Day 8 of each consecutive cycle.

RO6874281

Intervention Type: DRUG

Arms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part

Extension Part (Arm C): Atezolizumab, RO6874281

Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab once every 3 weeks until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months.

Note: no new participants are being enrolled in the arm at this time.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Arms A and B Atezolizumab will be administered at a dose of 840 milligrams (mg) prior to RO6874281 administration as an intravenous (IV) infusion on Days 1, 15, 29, and once in 2 weeks from Day 29 onwards. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

Arms C and D Atezolizumab will be administered at a dose of 1200mg as it is a Q3W schedule

RO6874281

Intervention Type: DRUG

Arms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part

Extension Part (Arm D): Atezolizumab, Bevacizumab, RO6874281

Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab and bevacizumab once every 3 weeks until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months.

Note: Arm D is closed for future enrollment

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Arms A and B Atezolizumab will be administered at a dose of 840 milligrams (mg) prior to RO6874281 administration as an intravenous (IV) infusion on Days 1, 15, 29, and once in 2 weeks from Day 29 onwards. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

Arms C and D Atezolizumab will be administered at a dose of 1200mg as it is a Q3W schedule

Bevacizumab

Intervention Type: DRUG

Arms A and B Bevacizumab will be administered at a dose of 10 milligrams per kilogram (mg/kg) after the atezolizumab administration, and prior to RO6874281 administration as an IV infusion on Days 15, 29, and once in 2 weeks from Day 29 onwards.

In Arm D, Bevacizumab will be administered at a dose of 15mg/kg on Day 8 of Cycle 2 and on Day 8 of each consecutive cycle.

RO6874281

Intervention Type: DRUG

Arms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part

Interventions

Atezolizumab

Arms A and B Atezolizumab will be administered at a dose of 840 milligrams (mg) prior to RO6874281 administration as an intravenous (IV) infusion on Days 1, 15, 29, and once in 2 weeks from Day 29 onwards. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

Arms C and D Atezolizumab will be administered at a dose of 1200mg as it is a Q3W schedule

Intervention Type: DRUG

Bevacizumab

Arms A and B Bevacizumab will be administered at a dose of 10 milligrams per kilogram (mg/kg) after the atezolizumab administration, and prior to RO6874281 administration as an IV infusion on Days 15, 29, and once in 2 weeks from Day 29 onwards.

In Arm D, Bevacizumab will be administered at a dose of 15mg/kg on Day 8 of Cycle 2 and on Day 8 of each consecutive cycle.

Intervention Type: DRUG

RO6874281

Arms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part.

In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part

Intervention Type: DRUG

Other Intervention Names

Tecentriq®; Avastin®; simlukafusp alfa

Eligibility Criteria

Inclusion Criteria

• Unresectable advanced and/or metastatic RCC with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic therapy, including treatment in the adjuvant setting
• During dose escalation only, an additional population with unresectable advanced and/or metastatic 2nd line RCC patients is allowed
• At least one tumor lesion with location accessible to biopsy per clinical judgment of the treating physician
• Consent to provide an archival tumor tissue sample (if available) and to undergo baseline and on treatment tumor biopsies for pharmacodynamic biomarker analysis
• Measurable disease, as defined by RECIST v1.1. At least one lesion accessible for biopsy
• Participants with unilateral pleural effusion are eligible if they fulfill both of the following: (a) New York Heart Association (NYHA) Class 1; (b) Global initiative for obstructive lung disease (GOLD) test level 1 (forced expiratory volume in 1 second [FEV1]/ forced vital capacity [FVC] less than [<] 0.7 and FEV1 greater than or equal to [>=] 80 percent [%] predicted after inhaled bronchodilator)

Adequate hematological function: neutrophil count of ≥1.5 ≥109 cells/L, platelet count of ≥100,000/≥L, Hb ≥9 g/dL (5.6 mmol/L), lymphocytes ≥0.8 ≥109 cells/L.

Exclusion Criteria

• Symptomatic or untreated central nervous system (CNS) metastases
• Participants with asymptomatic CNS metastases with previous or concomitant brain deficiencies, as defined in the protocol
• Participants with confirmed bilateral pleural effusion
• Episode of significant cardiovascular/cerebrovascular acute disease within 6 months prior to Cycle 1 Day 1
• Active or uncontrolled infections
• Human immunodeficiency virus (HIV) or active Hepatitis A, B, C, D and E virus (HAV, HBV, HCV, HDV and HEV) infection.
• Major surgery or significant traumatic injury <28 days prior to Cycle 1 Day 1 (excluding fine needle biopsies) or anticipation of the need for major surgery during study treatment
• Serious, non-healing wound; active ulcer; or untreated bone fracture
• Proteinuria as demonstrated by a urine protein to creatinine ratio (UPCR) of >=1.0 at screening
• History of, active or suspicion of autoimmune disease
• Concurrent use of high dose of systemic steroids. The use of inhaled, topical and ophthalmic steroids is allowed.

• 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

Yale Cancer Center; Medical Oncology

New Haven, Connecticut, United States

Northwestern Center for Clinical Research; Cancer Center

Chicago, Illinois, United States

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Herlev Hospital; Afdeling for Kræftbehandling

Herlev, , Denmark

Centre Léon Bérard - Centre régional de lutte contre le cancer Rhône-Alpes

Lyon, , France

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, , France

Universitätsklinikum Tübingen; Klinik für Urologie

Tübingen, , Germany

Uniklinikum, Comprehensive Cancer Center Mainfranken; Interdisziplinäres Studienzentrum mit ECTU

Würzburg, , Germany

Universita di Modena e Reggio Emilia;Dipartimento di Oncologia ed Ematologia

Modena, Emilia-Romagna, Italy

Fondazione IRCCS Policlinico San Matteo, Oncologia

Pavia, Lombardy, Italy

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, Spain

Hospital del Mar; Servicio de Oncologia

Barcelona, , Spain

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

Hospital Clínic i Provincial; Servicio de Oncología

Barcelona, , Spain

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, , Spain

Barts & London School of Med; Medical Oncology

London, , United Kingdom

The Christie

Manchester, , United Kingdom

Southampton General Hospital; Medical Oncology

Southampton, , United Kingdom

Countries

United States; Canada; Denmark; France; Germany; Italy; South Korea; Spain; United Kingdom

Other Identifiers

2016-003528-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP39365

Identifier Type: -

Identifier Source: org_study_id