A Phase 2 Clinical Trial Evaluating the Efficacy and Safety of Dual Immune Checkpoint Inhibition With Anti-PD-L1 (Atezolizumab) and Anti-TIGIT (Tiragolumab) in Cancer of Unknown Primary

NCT06754501 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2024-0210NCI-2024-10697
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the combination of atezolizumab and tiragolumab can help to control cancers of unknown primary. The safety and effects of this drug combination will also be studied

Conditions

Cancer

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 (1)

Treatment with Atezolizumab + Tiragolumab

EXPERIMENTAL

Drug: Atezolizumab; Drug: Tiragolumab

Interventions

Atezolizumab DRUG

Given by vein

Treatment with Atezolizumab + Tiragolumab

Tiragolumab DRUG

Given by vein

Treatment with 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 histopathological confirmed unresected, locally advanced, recurrent, or metastatic CUP. Patients must have undergone standard work-up to attempt to find the primary tumor prior to enrollment.
• Patients must be refractory or intolerant to at least one line of systemic chemotherapy or ineligible for cytotoxic chemotherapy.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for nonnodal 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.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of tiragolumab in combination with atezolizumab in patients \<18 years of age, children are excluded from this study.
• ECOG performance status of 0-1.
• Patients must have adequate organ and marrow function as defined below:
• ANC \> 1.5 x 109 /L (1500/L) without granulocyte colony-stimulating factor support.
• Lymphocyte count \> 0.5 x 109 /L (500/L).
• Platelet count \> 100 x 109 /L (100,000/L) without transfusion.
• Hemoglobin \> 90 g/L (9 g/dL).
• Patients may be transfused to meet this criterion.
• AST, ALT, and ALP \< 2.5 x upper limit of normal (ULN).
• Total bilirubin \< 1.5 x ULN with the following exception:
• Patients with known Gilbert disease: total bilirubin \< 3 x ULN.
• Creatinine clearance \> 45 mL/min (calculated using the Cockcroft-Gault formula).

You may not qualify if:

• Patients who have received treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, LAG-3inhibitor, or anti-CTLA-4 antibody, or any other antibody or drug that specifically targets Tcell co-stimulation or immune checkpoint pathways.
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e.,have residual toxicities \> NCI CTCAE v5.0 Grade 1) with the exception of alopecia, events that are not clinically significant, or asymptomatic laboratory abnormalities.
• Patients who are receiving any other investigational agents.
• 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 mmol/L, calcium \<12 mg/dL or corrected serum calcium \> ULN)
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the exceptions listed below:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator
• Strategic Alliance: collaborator

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

Conditions

Neoplasms

Interventions

atezolizumab; Tiragolumab

Study Officials

• Ryan Huey, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 30, 2024
• First Posted: December 31, 2024
• Study Start: April 11, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

US (1)