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

Running, not enrolling · Phase 2

Conditions studied: Cancer

In brief

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

Key facts

Study ID: NCT06754501
Run by: M.D. Anderson Cancer Center
People needed: 4
Starts: 2025-04-11
Expected to finish: 2029-07-01
Last updated by the study team: 2026-02-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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).
Serum albumin > 25 g/L (2.5 g/dL).
For patients not receiving therapeutic anticoagulation: INR and aPTT < 1.5 x ULN.
For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
Is able to provide archival or fresh tissues for correlative analysis with obtainable results.
Negative HIV test at screening with the following exception: individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4+ T cell count > 200/L, and have an undetectable viral load.
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:
Negative total hepatitis B core antibody (HBcAb).
Positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL.
The HBV DNA test will be performed only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test.

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.
'There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
Active tuberculosis Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
Patients who are taking prohibited medications as detailed in Appendix A.
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
Patients with psychiatric illness/social situations that would limit compliance with study requirements.
History of malignancy other than cancer of unknown primary within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.

Where it is running

The University of Texas M. D. Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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