Phase I/Ib Trial of TIraGolumab, AtEzolizumab, and RadScopal Radiation in Patients With Advanced Solid Malignancies (TIGER)
Overview
- Phase
- Phase 1
- Intervention
- Tiragolumab
- Conditions
- Advanced Solid Malignancies
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- Safety and Adverse Events (AEs)
- Status
- Active, not recruiting
- Last Updated
- 17 days ago
Overview
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.
Detailed Description
Primary Objectives: 1. To evaluate the safety of tiragolumab + atezolizumab + RadScopal™ XRT (Phase I). 2. To evaluate the efficacy of tiragolumab + atezolizumab + RadScopal™ XRT (Phase Ib). Secondary Objectives: 1. To compare the efficacy of tiragolumab + atezolizumab + RadScopal™ XRT to tiragolumab + atezolizumab and atezolizumab + RadScopal™ XRT. 2. To evaluate time-to-event outcomes of tiragolumab + atezolizumab + RadScopal™ XRT.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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:
Exclusion Criteria
- •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.
Arms & Interventions
PhI/PhIbP1 Tiragolumab + Atezolizumab + RadScopal XRT
Participants will be randomized to the trial using the Clinical Trial Conduct website
Intervention: Tiragolumab
PhI/PhIbP1 Tiragolumab + Atezolizumab + RadScopal XRT
Participants will be randomized to the trial using the Clinical Trial Conduct website
Intervention: Atezolizumab
PhI/PhIbP1 Tiragolumab + Atezolizumab + RadScopal XRT
Participants will be randomized to the trial using the Clinical Trial Conduct website
Intervention: Radiation Therapy
PhIbP2ArmC Tiragolumab + Atezolizumab
Participants will be randomized to the trial using the Clinical Trial Conduct website
Intervention: Atezolizumab
PhIbP2ArmA Atezolizumab + RadScopal XRT
Participants will be randomized to the trial using the Clinical Trial Conduct website
Intervention: Radiation Therapy
PhIbP2ArmB Tiragolumab + Atezolizumab + RadScopal XRT
Participants will be randomized to the trial using the Clinical Trial Conduct website
Intervention: Radiation Therapy
PhIbP2ArmB Tiragolumab + Atezolizumab + RadScopal XRT
Participants will be randomized to the trial using the Clinical Trial Conduct website
Intervention: Atezolizumab
PhIbP2ArmB Tiragolumab + Atezolizumab + RadScopal XRT
Participants will be randomized to the trial using the Clinical Trial Conduct website
Intervention: Tiragolumab
PhIbP2ArmC Tiragolumab + Atezolizumab
Participants will be randomized to the trial using the Clinical Trial Conduct website
Intervention: Tiragolumab
PhIbP2ArmA Atezolizumab + RadScopal XRT
Participants will be randomized to the trial using the Clinical Trial Conduct website
Intervention: Atezolizumab
Outcomes
Primary Outcomes
Safety and Adverse Events (AEs)
Time Frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0