Testing the Combination of Anti-cancer Drugs Atezolizumab and Tiragolumab in People With Advanced Stage Rare Cancers, RARE3 Trial

NCT05715281 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2023-00705IRB00159010561
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial tests how well atezolizumab works in combination with tiragolumab in treating patients with rare solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced stage). Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The study biopsy takes small pieces of cancer tissue from a tumor. The purpose of these biopsies is to compare the body's immune response against the tumor before and after treatment with the study drugs. Blood samples will also be collected for the study. The researchers will use the samples to learn more about how atezolizumab and tiragolumab work and which patients in the future might be most likely to respond to atezolizumab and tiragolumab. Using atezolizumab in combination with tiragolumab may help to shrink tumors in patients diagnosed with advanced stage rare solid-tumor cancers.

Conditions

Advanced Rare Malignant Solid Neoplasm; Rare Malignant Solid Neoplasm; Refractory Rare Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (3)

• Change in the proportion of active CD8+ T cells infiltrating the tumor

  At baseline and beginning of cycle 3

• Pharmacodynamic (PD) response rate

  The proportion of patients with a clinically promising increase in CD8+ T cell infiltration, defined as more than 1.5 standard deviations (SD) (as measured at baseline).

  At baseline, end of cycle 3, then every 2-4 cycles until disease progression

• Incidence of adverse events

  Reported using the common terminology criteria for adverse events version 5.0.

  Cycle 1 day 1 to 30 days after last dose

Secondary Outcomes (2)

• Objective tumor response rate (ORR)

  Up to 2 years

• Progression-free survival time

  Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years

Study Arms (1)

Treatment (atezolizumab, tiragolumab)

EXPERIMENTAL

Patients receive atezolizumab IV over 60 minutes and tiragolumab IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO at baseline, undergo biopsy at baseline and on study, and undergo CT and collection of blood samples throughout the study.

Biological: Atezolizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Drug: Tiragolumab

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Treatment (atezolizumab, tiragolumab)

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (atezolizumab, tiragolumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (atezolizumab, tiragolumab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (atezolizumab, tiragolumab)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (atezolizumab, tiragolumab)

Tiragolumab DRUG

Given IV

Treatment (atezolizumab, tiragolumab)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed rare solid tumors that have progressed on standard therapy or for whom there is no standard of care therapy
• Patients must not be eligible for a higher priority study that would be feasible for them to enroll in, such as a disease specific study of phase 2 or higher or a randomized study. Specifically, patients who are eligible for the PEP-CTN pediatric trial of atezolizumab and tiragolumab in children, adolescents, and young adults with SMARCB1- or SMARCA4-deficient tumors should be excluded
• Patients must have measurable disease as defined by RECIST v1.1, with at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with CT scan, MRI, or calipers by clinical exam)
• Patients must have a tumor site amenable to biopsy
• Age \>= 18 years. Because biopsies are mandatory on this trial, patients \< 18 years of age are excluded
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• International normalized ratio (INR) or activated partial thromboplastin time (aPTT) =\< 1.5 institutional upper limit of normal (ULN)
• Patients who receive therapeutic anticoagulation therapy should be on a stable dose
• Total bilirubin =\< 1.5 x institutional ULN (however, patients with known Gilbert disease who have serum bilirubin level of up to 3 mg/dl may be enrolled)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) =\< 2.5 x institutional ULN (AST and/or ALT =\< 5 x ULN for patients with liver involvement)
• Creatinine =\< 1.5 x institutional ULN OR creatinine clearance levels \>= 30 mL/min/1.73 m\^2 are permitted as the study agents are not secreted by the kidney
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

You may not qualify if:

• Patients who have had prior monoclonal antibody therapy must have completed that therapy \>= 5 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to start of treatment (minimum of 1 week between prior therapy and study enrollment)
• Patients must have recovered from clinically-significant adverse events of their most recent cancer immunotherapy to grade 1 or less, (with the exception of alopecia and lymphopenia)
• Patients who are receiving any other investigational agents
• Prior anti-TIGIT therapy is not allowed. However, other prior immune checkpoint inhibitor therapy is permitted
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies (i.e., antibodies with generic names ending in "ximab" or "zumab", respectively) or fusion proteins, not resolved by pre-medication or steroids, leading to subsequent treatment cessation. Patients with a history of allergic reaction to chimeric or humanized antibodies for which symptoms never recurred after subsequent re-challenge may be considered after careful medical history review
• Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone \[\> 10 mg/day\], cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to Cycle 1, Day 1
• Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
• The use of inhaled corticosteroids and systemic mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
• Patients with uncontrolled intercurrent illness, that would limit compliance with study requirements
• Pregnant women are excluded from this study because atezolizumab and tiragolumab are investigational agents with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, and because it is not known if tiragolumab can be excreted in human milk, breastfeeding should be discontinued if the mother is treated with atezolizumab
• History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
• Patients with autoimmune hyperthyroid disease not requiring immunosuppressive treatment may be eligible
• Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Interventions

atezolizumab; Biopsy; Specimen Handling; Tiragolumab

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jibran Ahmed

  National Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2023
• First Posted: February 8, 2023
• Study Start: September 26, 2023
• Primary Completion: October 6, 2025
• Study Completion (Estimated): November 21, 2026
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (3)