A Study of Atezolizumab Administered Alone or in Combination With Azacitidine in Participants With Myelodysplastic Syndromes

NCT ID: NCT02508870

Last Updated: 2019-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2019-06-10

Brief Summary

This is a multicenter, open-label, Phase 1b study of atezolizumab (anti-programmed death-ligand 1 [anti-PD-L1] monoclonal antibody) in participants who have hypomethylating agent (HMA)-naïve myelodysplastic syndromes (MDS) and are International Prognostic Scoring System-Revised (IPSS-R) intermediate/high/very high-risk, or have MDS relapsed or are refractory (R/R) to prior HMA therapy. The primary objectives of this study are to determine the safety and tolerability of atezolizumab therapy in these participant populations, including treatment in combination with azacitidine.

Conditions

Myelodysplastic Syndromes

Study Design

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

Study Groups

Cohort A: Atezolizumab - HMA R/R MDS

Participants with MDS who are HMA R/R will receive atezolizumab 1200 milligrams (mg) intravenous (IV) infusion every 3 weeks (Q3W) (21-day cycle). Treatment will continue for up to 17 cycles or until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first. Participants who achieve/maintain a partial response (PR) or hematological improvement (HI) after receiving 17 cycles of therapy may continue on study treatment beyond Cycle 17 until loss of clinical benefit.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participants will receive atezolizumab as per the schedule described in individual cohort.

Cohort B: Atezolizumab+Azacitidine - HMA R/R MDS

Induction: Participants with MDS who are HMA R/R will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 milligrams per square meter (mg/m\^2) subcutaneously (SC) on Days 1 to 7 of 28-day cycle, for 6 cycles. Maintenance: Participants who complete induction treatment will receive atezolizumab 1200 mg IV infusion Q3W (21-day cycle) for up to 8 additional cycles. Participants who achieve/maintain a PR or HI after completing the 8 cycles of atezolizumab maintenance therapy, may continue on study treatment until loss of clinical benefit.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participants will receive atezolizumab as per the schedule described in individual cohort.

Azacitidine

Intervention Type: DRUG

Participants will receive azacitidine as per the schedule described in individual cohort.

Cohort C1: Atezolizumab+Azacitidine - HMA-Naive MDS

Participants with MDS who are HMA-naive will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 mg/m\^2 SC on Days 1 to 7 of 28-day cycle, until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participants will receive atezolizumab as per the schedule described in individual cohort.

Azacitidine

Intervention Type: DRUG

Participants will receive azacitidine as per the schedule described in individual cohort.

Cohort C2: Atezolizumab+Azacitidine - HMA-Naive MDS

If the participants enrolled in Cohort C1 fulfil the dose limiting toxicity (DLT) criteria, then additional participants with MDS who are HMA-naïve will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 mg/m\^2 SC on Days 1 to 7 of 28-day cycle, until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participants will receive atezolizumab as per the schedule described in individual cohort.

Azacitidine

Intervention Type: DRUG

Participants will receive azacitidine as per the schedule described in individual cohort.

Cohort A2: Atezolizumab - HMA R/R MDS

If atezolizumab alone or in combination with azacitidine is found to be initially safe and tolerable in participants with HMA R/R MDS in both Cohorts A and B, then additional randomly assigned participants will receive atezolizumab 1200 mg IV infusion Q3W (21-day cycle). Treatment will continue for up to 17 cycles or until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first. Participants who achieve/maintain a PR or HI after receiving 17 cycles of therapy may continue on study treatment beyond Cycle 17 until loss of clinical benefit.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participants will receive atezolizumab as per the schedule described in individual cohort.

Cohort B2: Atezolizumab+Azacitidine - HMA R/R MDS

If atezolizumab alone or in combination with azacitidine is found to be initially safe and tolerable in participants with HMA R/R MDS in both Cohorts A and B, then additional randomly assigned participants will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 mg/m\^2 SC on Days 1 to 7 of 28-day cycle, for 6 cycles during induction. Participants who complete induction treatment will receive maintenance atezolizumab 1200 mg IV infusion Q3W (21-day cycle) for up to 8 additional cycles. Participants who achieve/maintain a PR or HI after completing the 8 cycles of atezolizumab maintenance therapy, may continue on study treatment until loss of clinical benefit.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Participants will receive atezolizumab as per the schedule described in individual cohort.

Azacitidine

Intervention Type: DRUG

Participants will receive azacitidine as per the schedule described in individual cohort.

Interventions

Atezolizumab

Participants will receive atezolizumab as per the schedule described in individual cohort.

Intervention Type: DRUG

Azacitidine

Participants will receive azacitidine as per the schedule described in individual cohort.

Intervention Type: DRUG

Other Intervention Names

Tecentriq; MPDL3280A; RO5541267; Vidaza

Eligibility Criteria

Inclusion Criteria

• Diagnosis of MDS (participants with therapy-related MDS are eligible)
• Eastern Cooperative Oncology Group (ECOG) performance status score less than or equal to (</=) 2
• Adequate end-organ function, as determined by laboratory tests obtained within 28 days prior to the first dose of study drug
• Willing and able to undergo a pre-treatment bone marrow biopsy and subsequent on-treatment bone marrow biopsies
• Women who are not postmenopausal or surgically sterile must have a negative serum pregnancy test result within 28 days prior to initiation of study drug
• For women of childbearing potential and men: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive measures

For participants in Cohorts A, A2, B, and B2:

• Progression at any time after initiation of azacitidine or decitabine treatment OR
• Failure to achieve complete or partial response or hematological improvement after at least six 4-week cycles of azacitidine or either four 4-week or four 6-week cycles of decitabine OR
• Relapse after initial complete or partial response or hematological improvement after six 4-week cycles of azacitidine or either four 4-week or four 6-week cycles of decitabine administered within the past 2 years

For participants in Cohorts C1 and C2:

• Must not have received prior treatment for MDS with any hypomethylating agent
• IPSS-R risk category of Intermediate, High, or Very High assessed at screening

Exclusion Criteria

• Participants with a diagnosis of MDS secondary to paroxysmal nocturnal hemoglobinuria (PNH), aplastic anemia, or another inherited bone marrow failure disorder
• Prior allogeneic stem cell transplant or solid organ transplant
• Pregnant or lactating, or intending to become pregnant during the study
• Investigational therapy within 28 days prior to initiation of study treatment
• Immunosuppressive therapy within 6 weeks of Cycle 1, Day 1
• Prior treatment with immune checkpoint blockade therapies (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed death-1 [PD-1] or anti-PD-L1) or immune agonists (anti-cluster of differentiation [CD] 137, anti-CD40, anti-OX40)
• Any other therapy or serious medical condition, as specified in the protocol, or abnormality in clinical laboratory tests that, in the investigator's judgement, precludes the participant's safe participation in and completion of the study
• Left ventricular ejection fraction (LVEF) </= 40 percent (%) at screening
• Planned major surgery during the study or within 4 weeks of Cycle 1, Day 1
• History of idiopathic pulmonary fibrosis, organizing pneumonitis, drug-induced pneumonitis, or idiopathic pneumonitis or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

• 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

City of Hope

Duarte, California, United States

Stanford University

Palo Alto, California, United States

University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, United States

University of Kansas Medical Center

Westwood, Kansas, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Nebraska Medical Center; UNMC Oncology/Hematology

Omaha, Nebraska, United States

Roswell Park Cancer Institute; Grace Cancer Drug Center

Buffalo, New York, United States

Montefiore Einstein Cancer Center

The Bronx, New York, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Medical University of South Carolina; Hollings Cancer Center

Charleston, South Carolina, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

University of Virginia Health System; Hematology/Oncology Division

Charlottesville, Virginia, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

References

Gerds AT, Scott BL, Greenberg P, Lin TL, Pollyea DA, Verma A, Dail M, Feng Y, Green C, Ma C, Medeiros BC, Yan M, Yousefi K, Donnellan W. Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome. Blood Adv. 2022 Feb 22;6(4):1152-1161. doi: 10.1182/bloodadvances.2021005240.

Reference Type: DERIVED

PMID: 34932793 (View on PubMed)

Other Identifiers

GO29754

Identifier Type: -

Identifier Source: org_study_id