Combination therapy with atezolizumab and tiragolumab for solid tumors

Open Label Phase 2 Basket Trial With Atezolizumab and Tiragolumab in Solid Tumors: TIRACAN

This study is testing a new combination treatment using two immune-boosting drugs for people with solid tumors, like melanoma and head and neck cancers, to see if it can help them fight their cancer better than current treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 97 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Medical Center Groningen (Academic / other)
• Drugs / interventions: atezolizumab, tiragolumab, methotrexate, cyclophosphamide, prednisone, immunotherapy
• Locations: 1 site (Groningen)
• Trial ID: NCT05483400 on ClinicalTrials.gov

What this trial studies

This open label phase II trial investigates the combination of the anti-PD-L1 antibody atezolizumab and the anti-TIGIT antibody tiragolumab in patients with various solid tumors, including head and neck neoplasms and metastatic melanoma. The study aims to enhance T cell responses against cancer by targeting both PD-L1 and TIGIT pathways, potentially improving treatment outcomes compared to single-agent therapies. Participants will be monitored for anti-tumor activity, safety, and tolerability of the combination therapy. The trial includes patients who are scheduled for surgery or have advanced disease that may benefit from this immunotherapy approach.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with measurable solid tumors, specifically localized head and neck squamous cell carcinoma, advanced or metastatic MSI-H cancer, or PD-1 resistant metastatic melanoma.

Not a fit: Patients with tumors that cannot be safely biopsied or those with significant comorbidities affecting organ function may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide improved treatment outcomes for patients with solid tumors that are resistant to current therapies.

How similar studies have performed: Previous studies have shown success with similar combination therapies in other cancer types, indicating potential for effectiveness in this trial as well.

Eligibility criteria

Inclusion Criteria:

* Tumor lesion(s) of which a histological biopsy can be safely obtained according to standard clinical care procedures.
* Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions should be discarded as target lesions.
* Participate in the GE-269-001 CD8 investigational imaging trial provided that there are slots is that trial.
* Signed informed consent.
* Age ≥18 at the time of signing informed consent.
* Life expectancy ≥12 weeks.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Adequate organ and bone marrow function defined as:

  1. hemoglobin ≥9.0 g/dL
  2. platelet count ≥100 x 109 /
  3. serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate \> 30 mL/min/1.73 m2. A 24-hour urine creatinine collection may substitute for the calculated creatinine clearance to meet eligibility criteria.
* Adequate hepatic function defined as:

  1. total bilirubin ≤1.5 x ULN (≤3 x ULN if liver tumor involvement); Patients with Gilbert's syndrome do not need to meet total bilirubin requirements, provided their total bilirubin is unchanged from their baseline. Gilbert's syndrome must be documented appropriately as past medical history,
  2. aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement)
  3. alanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement)
  4. alkaline phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if liver or bone tumor involvement).
* Ability to comply with the protocol.
* For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by the patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate (\< 1% per year) when used consistently and correctly).
* For the head and neck squamous cell carcinoma cohort specific eligibility criteria apply:

  1. clinical T2-4a, or node positive resectable HPV-unrelated HNSCC (oral cavity, larynx, hypopharynx, p16-negative oropharynx or p16 negative unknown primary)
  2. no evidence of distant metastases
  3. no previous RT to the head and neck region

Exclusion criteria:

* Signs or symptoms of infection within 2 weeks prior to atezolizumab and tiragolumab administration.
* Prior immune checkpoint inhibitor treatment, including but not limited to anti-PD1 and anti-PD-L1 antibodies (only for cohort 1, 2 and 4).
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use atezolizumab and tiragolumab, or that may affect the interpretation of the results or render the patient at high risk from complications.
* Pregnant or lactating women.
* Positive test for HIV, active hepatitis B (chronic or acute defined by positive hepatitis B surface antigen (HBsAg) during screening) or hepatitis C. Patients with a medical history of hepatitis B infection (defined as a positive hepatitis B core antibody (HBcAb) and absence of an HBsAg) are eligible for this study. Patients who test positive for hepatitis C antibodies are only eligible with a negative hepatitis C RNA PCR.
* Acute or chronic active Epstein-Barr virus (EBV) infection at screening EBV status should be assessed by EBV serology (e.g., anti-VCA IgM and IgG, anti-EA IgG, anti-EBNA IgG) and EBV PCR (plasma or serum). If EBV serology results indicate prior EBV infection, patients must have a negative EBV PCR (plasma or serum) to be eligible for the study.
* Active tuberculosis.
* Treatment with systemic immunostimulatory agents (including but not limited to IFNs, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to the first full dose of atezolizumab and tiragolumab.
* Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to cycle 1, day 1, with the exception of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for subjects with orthostatic hypotension, low-dose supplemental corticosteroids for adrenocortical insufficiency and topical steroids are allowed. Medications (e.g., a one-time dose of dexamethasone for nausea) may be allowed in the study after discussion with and approval by the principal investigator.
* Brain metastases and leptomengeal metastases.

Where this trial is running

Groningen

• University Medical Center Groningen — Groningen, Netherlands (Recruiting)

Study contacts

• Principal investigator: Derk JA de Groot, MD PhD — University Medical Center Groningen
• Study coordinator: Derk JA de Groot, Md PhD

Conditions Head and Neck Neoplasms; MSI-H Cancer; Melanoma; atezolizumab; tiragolumab