Phase I/Ib Trial of TIraGolumab, AtEzolizumab, and RadScopal Radiation in Patients With Advanced Solid Malignancies (TIGER)

NCT06760481 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-0309NCI-2024-10794
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, Phase I/Ib study investigating the safety and efficacy of tiragolumab + atezolizumab + RadScopal™ XRT in patients with metastatic solid malignancies.

Conditions

Advanced Solid Malignancies

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (4)

PhI/PhIbP1 Tiragolumab + Atezolizumab + RadScopal XRT

EXPERIMENTAL

Participants will be randomized to the trial using the Clinical Trial Conduct website

Drug: Tiragolumab; Drug: Atezolizumab; Radiation: Radiation Therapy

PhIbP2ArmA Atezolizumab + RadScopal XRT

EXPERIMENTAL

Participants will be randomized to the trial using the Clinical Trial Conduct website

Drug: Atezolizumab; Radiation: Radiation Therapy

PhIbP2ArmB Tiragolumab + Atezolizumab + RadScopal XRT

EXPERIMENTAL

Participants will be randomized to the trial using the Clinical Trial Conduct website

Drug: Tiragolumab; Drug: Atezolizumab; Radiation: Radiation Therapy

PhIbP2ArmC Tiragolumab + Atezolizumab

EXPERIMENTAL

Participants will be randomized to the trial using the Clinical Trial Conduct website

Drug: Tiragolumab; Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Given by IV

PhI/PhIbP1 Tiragolumab + Atezolizumab + RadScopal XRT; PhIbP2ArmA Atezolizumab + RadScopal XRT; PhIbP2ArmB Tiragolumab + Atezolizumab + RadScopal XRT; PhIbP2ArmC Tiragolumab + Atezolizumab

Radiation Therapy RADIATION

Given by IV

PhI/PhIbP1 Tiragolumab + Atezolizumab + RadScopal XRT; PhIbP2ArmA Atezolizumab + RadScopal XRT; PhIbP2ArmB Tiragolumab + Atezolizumab + RadScopal XRT

Tiragolumab DRUG

Given by IV

PhI/PhIbP1 Tiragolumab + Atezolizumab + RadScopal XRT; PhIbP2ArmB Tiragolumab + Atezolizumab + RadScopal XRT; PhIbP2ArmC Tiragolumab + Atezolizumab

Eligibility Criteria

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

You may qualify if:

• Aged ≥18 years at the time of informed consent form signing Patients must have a histologically confirmed metastatic or unresectable solid tumor.
• All histological types will be eligible, with preference given to squamous histologies including lung, cervical, head and neck, and esophageal cancers.
• Patients must not have available standard of care options or available standard of care option(s) are deemed to be less effective than the clinical trial alternative by the treating physician.
• Life expectancy ≤3 months.
• Prior anti-PD-1/PD-L1 therapy is allowed.
• Patients will be eligible regardless of the number of prior lines of therapy.
• Patients must have measurable disease per the RECIST v1.1.
• Patients must have at least three active lesions, with at least one lesion amenable to HD-XRT (50 Gy in 4 fractions or 30 Gy in 5 fractions) as determined by the radiation oncologist. Repeat radiation with LD-XRT to previously irradiated sites will be allowed at the discretion of the investigator or treating radiation oncologist.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix A).
• Adequate organ and marrow function as defined below:
• Table 1. Adequate Organ Function Laboratory Values Systemic Function Test - Laboratory Value Hematologic ANC ≥1500/L Platelets ≥100,000/L Hemoglobin ≥9.0 g/dL Lymphocyte count ≥500/L Renal CrCl by Cockcroft-Gault formula
• ≥45 mL/min Hepatic Total bilirubin ≤1.5 × ULN (Patients with known Gilbert disease: ≤3 × ULN) AST, ALT, and ALP ≤2.5 × ULN (≤5 × ULN for patients with liver metastases) Albumin ≥2.5 g/dL Coagulation PT/INR aPTT ≤1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• aPTT=activated partial thromboplastin; ALP=alkaline phosphatase; ALT=alanine aminotransferase; ANC=absolute neutrophil count; AST=aspartate aminotransferase; CrCl=creatinine clearance; INR=international normalized ratio; PT=prothrombin time; ULN=upper limit of normal.
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
• Negative hepatitis B surface antigen (HBsAg) test at screening. Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following:

You may not qualify if:

• History of leptomeningeal disease. ● Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
• Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmo1/L, calcium \>12 mg/dL or corrected serum calcium \> ULN).
• Active tuberculosis.
• Received XRT within 14 days prior to study treatment initiation.
• Received anticancer systemic therapies (including chemotherapy, immunotherapy, targeted therapy, or other modalities such as investigational agents) within 21 days or 5 half-lives of the drug, whichever is shorter.
• Prior XRT to the target lesion(s) selected for HD-XRT. Previous radiation to LDXRT target lesions is allowed per investigator or treating radiation oncologist discretion.
• Unresolved Grade ≥2 AEs from prior anticancer therapy. Patients with Grade 2 neuropathy, alopecia, or other non-relevant AEs may be deemed eligible at the discretion of the principal investigator (PI).
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
• Requirement for systemic IV antibiotics for infection within 3 days prior to study treatment initiation. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment, within 90 days after the final dose of tiragolumab, or within 5 months after the final dose of atezolizumab.
• Positive Epstein-Barr virus (EBV) viral capsid antigen IgM test at screening. An EBV polymerase chain reaction (PCR) test should be performed as clinically indicated to screen for acute infection or suspected chronic active infection. Patients with a positive EBV PCR test are excluded.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, renal failure, cardiac arrhythmia, or psychiatric illness that would adversely impact the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Interventions

Tiragolumab; atezolizumab; Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Ecaterina Dumbrava, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 31, 2024
• First Posted: January 6, 2025
• Study Start: April 13, 2025
• Primary Completion (Estimated): September 15, 2028
• Study Completion (Estimated): September 15, 2030
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)