A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors

NCT02650713 | Completed Phase 1

• 3 other identifiers: WP29945RG78022015-003771-30
• Study Type: interventional
• Target: 228
• Locations: 7 countries
• Sites: 24

Brief Summary

This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab. Part I of the study is subdivided into parts IA and IB. Part IA is dose escalation with a starting dose of 5 mg of RO6958688 given QW (once a week) and a fixed, flat dose of 1200 mg given Q3W (every 3 weeks) of atezolizumab, to evaluate the safety and determine the MTD of RO6958688 in combination with atezolizumab. Part IB is a dose/schedule finding part that will explore different administration schedules of RO6958688 in combination with atezolizumab (1200 mg Q3W) to establish the appropriate dose/schedule of RO6958688 in combination with atezolizumab.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Number of Participants with Adverse Events (AEs)

  Baseline up to 60 months

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

  Day 1 up to Day 21

• Maximum-Tolerated Dose (MTD) of RO6958688

  Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation

• Recommended Phase II Dose (RP2D) of RO6958688

  Day 1 up to 60 months

Secondary Outcomes (16)

• Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688

  Baseline up to 60 months

• PK: Volume of Distribution at Steady State (Vss) of RO6958688

  Baseline up to 60 months

• PK: Maximum Serum Concentration (Cmax) of RO6958688

  Baseline up to 60 months

• PK: Clearance (CL) of RO6958688

  Baseline up to 60 months

• PK: AUC of Atezolizumab

  Baseline up to 60 months

Study Arms (2)

Dose-Escalation (Part IA): RO6958688 + Atezolizumab

EXPERIMENTAL

Participants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W). RO6958688 dosage will not exceed the MTD if defined in the BP29541 study.

Drug: Atezolizumab; Drug: RO6958688

Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab

EXPERIMENTAL

Part IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of: Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688. Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first.

Drug: Atezolizumab; Drug: RO6958688

Interventions

Atezolizumab DRUG

Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.

Also known as: Tecentriq

Dose-Escalation (Part IA): RO6958688 + Atezolizumab; Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab

RO6958688 DRUG

RO6958688 is administered by IV infusion In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle. In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W. Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower.

Dose-Escalation (Part IA): RO6958688 + Atezolizumab; Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab

Eligibility Criteria

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

You may qualify if:

• Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor lesion of accessible non-critical location to biopsy, in participants who have progressed on a standard therapy, are intolerant to standard therapy, and/or are non-amenable to standard therapy
• Radiologically measurable and clinically evaluable disease (as per RECIST v1.1)
• Life expectancy (in the opinion of the investigator) of at least 12 weeks and lactate dehydrogenase (LDH) levels \</= 2.5 ULN (upper limit of normal)
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
• All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade \</= 1 or returned to baseline except alopecia (any grade) and Grade 2 peripheral neuropathy
• Adequate hematological, liver, and renal function
• Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women \</= 2 years after start of menopause (menopause is defined as amenorrhea for more than 2 years)
• Participants must agree to remain abstinent or be willing to use effective methods of contraception as defined in the protocol
• Participants with non-colorectal cancer should have confirmed CEA expression in tumor tissue. For colorectal cancer (CRC), the CEA assessment should be performed but the result is not required for participant selection

You may not qualify if:

• Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
• Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 2 weeks prior to enrollment
• Leptomeningeal disease
• Participants with paraspinal, paratracheal, and mediastinal pathological lesions larger than 2 cm unless they are previously irradiated
• Malignancies within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
• Significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results
• Uncontrolled hypertension, unstable angina, congestive heart failure (CHF), serious cardiac arrhythmia requiring treatment history of myocardial infarction within 6 months of enrollment
• Administration of a live, attenuated vaccine within 28 days before Cycle 1 Day 1 or anticipation that such a live attenuated vaccine will be required during the study
• Human Inmmunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C (HCV)
• Severe infections within 28 days prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia or active tuberculosis
• Received oral or intravenous (IV) antibiotics within 14 days prior to Day 1
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
• Major surgery or significant traumatic injury less than 28 days prior to Cycle 1 Day 1 (excluding biopsies) or anticipation of the need for major surgery during study treatment
• Known history of autoimmune disease as defined in the protocol
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis (including drug induced) on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (24)

UCLA Cancer Center

Santa Monica, California, 90404, United States

Location

Stanford Comprehensive Cancer Center

Stanford, California, 94305, United States

Location

University Of Colorado

Aurora, Colorado, 80045, United States

Location

Smilow Cancer Hospital at Yale- New Haven Oncology Investigational Drug Pharmacy

New Haven, Connecticut, 06510, United States

Location

Dana Farber Can Ins

Boston, Massachusetts, 02215, United States

Location

Columbia Univ Med Ctr

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Sarah Cannon Cancer Center

Germantown, Tennessee, 38138, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

Rigshospitalet; Onkologisk Klinik

København Ø, 2100, Denmark

Location

Centre Leon Berard; Departement Oncologie Medicale

Lyon, 69373, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

IRCCS IST. Tumori Fondaz. Pascale; S.C. Oncologia Medica,Melanoma,Immunoterapia E Terapie Innovative

Napoli, Campania, 80131, Italy

Location

Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica

Siena, Tuscany, 53100, Italy

Location

Antoni Van Leeuwenhoek Ziekenhuis; Gastro-Enterologie

Amsterdam, 1066 CX, Netherlands

Location

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, 31008, 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-FJD, Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, 28041, Spain

Location

START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

Madrid, 28050, Spain

Location

Related Publications (1)

• Martinez-Sabadell A, Morancho B, Rius Ruiz I, Roman Alonso M, Ovejero Romero P, Escorihuela M, Chicote I, Palmer HG, Nonell L, Alemany-Chavarria M, Klein C, Bacac M, Arribas J, Arenas EJ. The target antigen determines the mechanism of acquired resistance to T cell-based therapies. Cell Rep. 2022 Oct 18;41(3):111430. doi: 10.1016/j.celrep.2022.111430.

  PMID: 36261015 DERIVED

MeSH Terms

Interventions

atezolizumab

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 8, 2016
• Study Start: January 7, 2016
• Primary Completion: January 13, 2020
• Study Completion: January 13, 2020
• Last Updated: February 12, 2020

Record last verified: 2020-02

Locations

NL (1); CA (1); DK (1); FR (2); US (11); IT (2); ES (6)