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

NCT05483400 | Recruiting Phase 2 DMC

• 1 other identifier: 10389
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

In this open label phase II trial combination therapy with the anti-PD-L1 antibody atezolizumab and the anti-TIGIT antibody tiragolumab will be investigated in patients with localized HNSCC who will undergo surgery, advanced or metastatic MSI-H cancer, PD-1 resistant metastatic melanoma, and patients with a locally advanced or metastatic solid tumor who, in the opinion of the investigator, based on available clinical data, may benefit from treatment with anti-PD-L1 and anti-TIGIT immunotherapy.

Conditions

Head and Neck Neoplasms; MSI-H Cancer; Melanoma

Keywords

atezolizumab; tiragolumab

Outcome Measures

Primary Outcomes (2)

• Pathologic response in cohort 1

  pTR is defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (\<10%), pTR-1 (10%-49%), and pTR-2 (≥50%).

  At the time of resection of the tumor which is day 36-43 after the first course of therapy

• Best overall response rate in cohort 2-4

  Overall response rate according to (i)RECIST 1.1

  From date of randomization until the date of first documented progression or after a maximum of two years of treatment

Secondary Outcomes (6)

• Clinical safety

  Through study completion, a maximum of 24 months

• Disease free survival in cohort 1

  The time from surgery to the time of local, regional or distant disease recurrence or death, whichever comes first put or 60 months

• Progression free survival

  PFS is defined as the time from the first full treatment dose of atezolizumab and tiragolumab to time of disease progression or death due to any cause, whichever occurs first within a timeframe of 60 months

• Overall response rate

  ORR is defined as the proportion of subjects whose best overall response is either a PR or CR, as assessed by the investigator during a maximum of 24 months on treatment

• Duration of objective response

  PFS is defined as the time from the first full treatment dose of atezolizumab and tiragolumab to time of disease progression per (i)RECIST as determined by the investigator or death due to any cause, whichever occurs first during a maximum of 60 months

Study Arms (4)

Localized Head and Neck Squamous Cell Cancer

EXPERIMENTAL

three weekly tiragolumab 1200 mg intravenous plus tiragolumab 600 mg intravenous

Drug: Tiragolumab and atezolizumab

Advanced or Metastatic dMMR/MSI Cancer

EXPERIMENTAL

three weekly tiragolumab 1200 mg intravenous plus tiragolumab 600 mg intravenous

Drug: Tiragolumab and atezolizumab

Anti-PD-1 Antibody Resistant Metastatic Melanoma

EXPERIMENTAL

three weekly tiragolumab 1200 mg intravenous plus tiragolumab 600 mg intravenous

Drug: Tiragolumab and atezolizumab

Basket

EXPERIMENTAL

three weekly tiragolumab 1200 mg intravenous plus tiragolumab 600 mg intravenous

Drug: Tiragolumab and atezolizumab

Interventions

Tiragolumab and atezolizumab DRUG

three weekly tiragolumab 1200 mg intravenous plus tiragolumab 600 mg intravenous.

Advanced or Metastatic dMMR/MSI Cancer; Anti-PD-1 Antibody Resistant Metastatic Melanoma; Basket; Localized Head and Neck Squamous Cell Cancer

Eligibility Criteria

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

You may qualify if:

• 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:
• hemoglobin ≥9.0 g/dL
• platelet count ≥100 x 109 /
• 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:
• 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,
• aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement)
• alanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms; Melanoma

Interventions

Tiragolumab; atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Derk JA de Groot, MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Derk JA de Groot, Md PhD

CONTACT

+31503612821; d.j.a.de.groot@umcg.nl

Daan G Knapen, MD

CONTACT

+31503612821; d.g.knapen@umcg.nl

Study Design

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

Model Details: Simon 2 stage design with 4 cohorts.

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: August 2, 2022
• Study Start: October 18, 2023
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)