TIRACAN; Open label phase 2 basket trial with Atezolizumab and Tiragolumab in solid tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Oct 2023 → ongoing

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512616-21-00

EudraCT number

2021-006894-48

ClinicalTrials.gov

NCT05483400

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

1. To determine pathological response rate (pTR) in patients in cohort 1 with localized HNSCC.
2. To determine the response rates in patients in cohort 2, 3, and 4 with advanced or metastatic dMMR/MSI cancer, PD-1 resistant metastatic melanoma, and with a locally advanced or metastatic solid tumor who, in the investigator’s opinion, based on available clinical data, may benefit from treatment with atezolizumab and tiragolumab.

Secondary objectives 5

1. To determine safety of atezolizumab and tiragolumab in patients with localized HNSCC and advanced or metastatic dMMR/MSI cancer, anti-PD-1 resistant metastatic melanoma and patients with a locally advanced or metastatic solid tumor whom, in the opinion of the investigator, based on available clinical data, may benefit from treatment with anti- PD-L1 immunotherapy.
2. To assess disease free survival (DFS) in patients with localized HNSCC. Events are defined as local recurrence, regional recurrence, distant metastases and death from any cause.
3. Evaluation of ORR, PFS and duration of objective response (DOR) according to (i)RECIST, as assessed by the investigator in cohort 2, 3 and 4.
4. Correlate ctDNA, TIGIT, PD-1, PD-L1 and CD8 IHC expression in tumor tissue with pathological response in cohort 1, and RECIST1.1 and iRECIST in cohort 2, 3 and 4.
5. Correlate presence of/kinetics of ctDNA in blood with with pathological response in cohort 1, and RECIST1.1 and iRECIST in cohort 2, 3 and 4.

Conditions and MedDRA coding

HNSCC, metastatic deficient mismatch repair (dMMR)/MSI-high (MSI-H) tumors, irresectable or metastatic melanoma, locally advanced or metastatic solid tumor

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Tumor lesion(s) of which a histological biopsy can be safely obtained according to standard clinical care procedures.
2. Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions should be discarded as target lesions.
3. Participate in the GE-269-001 CD8 investigational imaging trial provided that there are slots is that trial.
4. Signed informed consent.
5. Age ≥18 at the time of signing informed consent.
6. Life expectancy ≥12 weeks.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
8. Adequate organ and bone marrow function as defined below: o Hemoglobin ≥9.0 g/dL. o Platelet count ≥100 x 109 /L. o 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. o Adequate hepatic function: ▪ 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) ▪ Alkaline phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if liver or bone tumor involvement)
9. Ability to comply with the protocol.
10. 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.
11. For the head and neck squamous cell carcinoma cohort specific eligibility criteria apply • clinical T2-4a, or node positive resectable HPV-unrelated HNSCC (oral cavity, larynx, hypopharynx, p16-negative oropharynx or p16 negative unknown primary) • no evidence of distant metastases. • no previous radiotherapy to the head and neck region.

Exclusion criteria 12

1. Signs or symptoms of infection within 2 weeks prior to atezolizumab and tiragolumab administration.
2. Prior immune checkpoint inhibitor treatment, including but not limited to anti-PD1 and anti- PD-L1 antibodies (only for cohort 1, 2 and 4).
3. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
4. 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.
5. Pregnant or lactating women.
6. 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.
7. Acute or chronic active 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.
8. Active tuberculosis.
9. 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.
10. 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.
11. 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 (PI).
12. Brain metastases, leptomeningeal metastases.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pathologic response of the primary tumor (pTR) in patients with HNSCC and ORR according to (i)RECIST 1.1 in patients with advanced or metastatic dMMR/MSI cancer, metastatic melanoma and patients with a locally advanced or metastatic solid tumor whom, in the opinion of the investigator, based on available clinical data, may benefit from treatment with anti-PD-L1 immunotherapy.

Secondary endpoints 4

1. Safety assessment through: o Incidence, nature and severity of adverse events, including protocol-defined events of special interest such as described in section 10.1.6, graded according to NCI CTCAE 5.0 o Changes in laboratory test results, vital signs and physical findings.
2. Assessment of DFS in patients with HNSCC. o DFS is defined as the time from surgery to the time of local, regional or distant disease recurrence or death, whichever comes first.
3. Evaluation of ORR, PFS and DOR according to (i)RECIST, as assessed by the investigator for cohort 2, 3 and 4.
4. The correlation between TIGIT, PD-1, PD-L1 and CD8 IHC expression on tumor tissue provided prior to start of treatment and inflammatory infiltrate with radiographic (CT or MRI) in cohort 2, 3, and pathologic response pTR in cohort 1 and 2.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

D.J.A. de Groot

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

D.J.A. de Groot

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications