A Study of Intravenous (IV) Cergutuzumab Amunaleukin and Atezolizumab in Combination in Participants With Locally Advanced and/or Metastatic Solid Tumors

NCT02350673 | Completed Phase 1

• 2 other identifiers: BP294352014-000948-14
• Study Type: interventional
• Target: 70
• Locations: 6 countries
• Sites: 14

Brief Summary

This is an open-label, multi-center, Phase Ib clinical study of cergutuzumab amunaleukin, in combination with atezolizumab, to investigate the safety, pharmacokinetics, and therapeutic activity in participants with locally advanced and/or metastatic carcinoembryonic antigen (CEA)-positive solid tumors, whose disease has progressed on or who are intolerant to the standard of care therapy. Enrolled participants who continue treatment will be treated until loss of clinical benefit, unacceptable toxicities, or withdrawal of consent. The study will include 2 parts: a dose-escalation Part I and a dose expansion Part II. The anticipated treatment period is 24 months for both cergutuzumab amunaleukin and atezolizumab and may be modified if emerging data suggest a benefit.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (10)

• Number of Participants with Dose-Limiting Toxicities

  Day 1 up to Day 21

• MTD of Cergutuzumab Amunaleukin

  Day 1 up to Day 21

• Recommended Phase II Dose of Cergutuzumab Amunaleukin

  Day 1 up to Day 21

• Percentage of Participants with Adverse Events

  Baseline up to 30 months

• Percentage of Participants with Infusion-Related Reactions

  Baseline up to 30 months

• Percentage of Participants with Seroconversion of Autoantibodies

  Seroconversion is defined as the presence of at least one of the following autoantibodies: anti-nuclear antibody, antidouble-stranded deoxyribose nucleic acid (DNA), cytoplasmic anti-neutrophil cytoplasmic antibody, and perinuclear anti-neutrophil cytoplasmic antibody.

  Screening up to 30 months (assessed at Screening, predose [Hour 0] on Day 1 of Cycles 2, 4, and 6, and every 3 months after Cycle 6 up to approximately 30 months [cycle length= 14 or 21 days])

• Forced Expiratory Volume

  Screening (up to 28 days prior to Cycle 1 Day 1)

• Forced Vital Capacity

  Screening (up to 28 days prior to Cycle 1 Day 1)

• Percentage of Participants with Anti-Atezolizumab Antibodies

  Day 1 Cycle 1 up to 30 months (assessed at Day 1 of Cycles 1, 2, 3, 4, study completion/early discontinuation [up to 30 months], 28 and 120 days post last infusion up to approximately 30 months [cycle length = 14 or 21 days])

• Percentage of Participants with Anti-Cergutuzumab Amunaleukin Antibodies

  Day 1 Cycle 1 up to 30 months (assessed at Day 1 of Cycles 1, 2, 3, 4, study completion/early discontinuation [up to 30 months], 28 and 120 days post last infusion up to approximately 30 months [cycle length = 14 or 21 days])

Secondary Outcomes (19)

• Percentage of Participants with Objective Response of Complete Response (CR) or Partial Response (PR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 as Determined by the Investigator

  Screening up to disease progression or death due to any cause whichever occurs first (assessed at Weeks 8 and 12, every 8 weeks thereafter for the first year, and every 12 weeks thereafter up to approximately 30 months overall)

• Percentage of Participants with Disease Control (Tumor Response of CR or PR or Stable Disease [SD]) Based on RECIST v1.1 as Determined by the Investigator

  Screening up to disease progression or death due to any cause whichever occurs first (assessed at Weeks 8 and 12, every 8 weeks thereafter for the first year, and every 12 weeks thereafter up to approximately 30 months overall)

• Percentage of Participants with SD, Based on RECIST v1.1 as Determined by the Investigator

  Screening up to disease progression or death due to any cause whichever occurs first (assessed at Weeks 8 and 12, every 8 weeks thereafter for the first year, and every 12 weeks thereafter up to approximately 30 months overall)

• Progression-Free Survival Based on RECIST v1.1 as Determined by the Investigator

  Screening up to disease progression or death due to any cause whichever occurs first (assessed at Weeks 8 and 12, every 8 weeks thereafter for the first year, and every 12 weeks thereafter up to approximately 30 months overall)

• Overall Survival

  Screening up to death due to any cause (up to approximately 30 months overall)

Study Arms (2)

Cergutuzumab+Atezolizumab (Part I)

EXPERIMENTAL

Participants will receive escalated IV doses of cergutuzumab amunaleukin in combination with atezolizumab. This is a Part I dose escalation phase of the study. Cergutuzumab amunaleukin will be escalated from a starting dose of 6 milligrams (mg) and dosing schedules of every week (qw) and every 2 weeks (q2w) may be explored. Atezolizumab will be administered in fixed flat doses of either 840 mg q2w or 1200 mg every 3 weeks (q3w). Treatment will be continued until loss of clinical benefit, unacceptable toxicities, or withdrawal of consent for a maximum treatment period of 24 months for both cergutuzumab amunaleukin and atezolizumab and may be modified if emerging data suggest longer treatment period is needed.

Drug: Atezolizumab; Drug: Cergutuzumab Amunaleukin

Cergutuzumab +Atezolizumab (Part II)

EXPERIMENTAL

This is a Part II expansion phase of the study. Participants will receive cergutuzumab amunaleukin at maximum tolerated dose (MTD) (or recommended dose) identified during Part I in combination with atezolizumab. Treatment will be continued until loss of clinical benefit, unacceptable toxicities, or withdrawal of consent for a maximum treatment period of 24 months for both cergutuzumab amunaleukin and atezolizumab and may be modified if emerging data suggest longer treatment period is needed.

Drug: Atezolizumab; Drug: Cergutuzumab Amunaleukin

Interventions

Atezolizumab DRUG

Participants will receive atezolizumab IV infusion at doses of 800 mg q2w or 1200 mg q3w.

Also known as: MPDL3280A, Tecentriq®

Cergutuzumab +Atezolizumab (Part II); Cergutuzumab+Atezolizumab (Part I)

Cergutuzumab Amunaleukin DRUG

Participants will receive cergutuzumab amunaleukin IV infusion at escalated doses and at different dosing schedules in Part I and at MTD (or recommended dose) in Part II.

Also known as: RO6895882, CEA-IL2v

Cergutuzumab +Atezolizumab (Part II); Cergutuzumab+Atezolizumab (Part I)

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 non-critical location accessible to biopsy (with exception of non-small cell lung cancer \[NSCLC\] participants), and with confirmed progression at baseline that has progressed on, or participant is intolerant to, the standard of care therapy
• Radiologically measurable and clinically evaluable disease as per RECIST v1.1
• Life expectancy, in the opinion of the investigator, greater than or equal to (\>=) 12 weeks
• Eastern Cooperative Oncology Group Performance Status 0-1
• All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade less than or equal to (\<=) 1, except alopecia (any grade) and Grade 2 peripheral neuropathy
• Adequate cardiac, hematological, liver and renal function
• Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women \<= 2 years after menopause
• For women who are not postmenopausal and have not undergone surgical sterilization: agreement to remain abstinent or use two adequate non-hormonal methods of contraception including at least one method with a failure rate of \<1% per year during the treatment period and for at least five months after the last dose of atezolizumab and at least four months after the last dose of cergutuzumab amunaleukin, whichever is the longest
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
• Locally or centrally confirmed CEA expression in archival tumor tissue

You may not qualify if:

• Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments; participants with a history of treated asymptomatic CNS metastases are eligible
• 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 \>= 2 weeks prior to randomization
• Leptomeningeal disease
• Participants with an active second malignancy (other than non-melanoma skin cancer or cervical carcinoma in situ). Participants who have a history of malignancy are not considered to have an active malignancy if they have completed therapy and are considered by their treating physician to be at \<= 30 percent (%) risk for relapse
• Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, and known autoimmune diseases
• Participants with bilateral pleural effusion and NSCLC participants with uni- or bilateral effusion confirmed at screening by X-ray are not eligible
• Uncontrolled hypertension, unstable angina, congestive heart failure of any NYHA classification stage greater than (\>) 2, serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of enrollment
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only. Participants must not receive live, attenuated influenza vaccine within 4 weeks prior to Cycle 1, Day 1, at any time during the study or 5 months after the last dose of atezolizumab
• Known Human Immunodeficiency Virus (HIV)
• Active hepatitis B (HBV) or hepatitis C (HCV) infection
• Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Received oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1, Day 1. Participants receiving prophylactic antibiotics (for prevention of a urinary tract infection chronic obstructive pulmonary disease) are eligible
• 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 the first cergutuzumab amunaleukin infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
• Dementia or altered mental status that would prohibit informed consent

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (14)

Yale Cancer Center; Medical Oncology

New Haven, Connecticut, 06520, 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

SCRI-Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9, Canada

Location

Herlev Hospital; Onkologisk afdeling

Herlev, 2730, Denmark

Location

Rigshospitalet; Onkologisk Klinik

København Ø, 2100, Denmark

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Clinica Universitaria de Navarra; Servicio de oncología

Pamplona, Navarre, 31008, 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

CHUV; Departement d'Oncologie

Lausanne, 1011, Switzerland

Location

MeSH Terms

Interventions

atezolizumab

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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2015
• First Posted: January 30, 2015
• Study Start: June 29, 2015
• Primary Completion: December 16, 2019
• Study Completion: December 16, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

CA (1); CH (1); NL (2); ES (4); DK (2); US (4)