Trial Title:
Open Label Phase 2 Basket Trial With Atezolizumab and Tiragolumab in Solid Tumors
NCT ID:
NCT05483400
Condition:
Head and Neck Neoplasms
MSI-H Cancer
Melanoma
Conditions: Official terms:
Head and Neck Neoplasms
Atezolizumab
Conditions: Keywords:
atezolizumab
tiragolumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Intervention model description:
Simon 2 stage design with 4 cohorts.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tiragolumab and atezolizumab
Description:
three weekly tiragolumab 1200 mg intravenous plus tiragolumab 600 mg intravenous.
Arm group label:
Advanced or Metastatic dMMR/MSI Cancer
Arm group label:
Anti-PD-1 Antibody Resistant Metastatic Melanoma
Arm group label:
Basket
Arm group label:
Localized Head and Neck Squamous Cell Cancer
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.
Detailed description:
Rationale:
Tumor immunotherapy has demonstrated that therapies focused on enhancing T cell responses
against cancer can result in a significant survival benefit in subjects with advanced
stages of cancer. The most frequently used immunotherapy drugs bind to the Programmed
death-ligand 1 (PD-L1) or programmed death protein 1 (PD-1). This binding interrupts the
PD-L1/PD-1 pathway which inhibits an anti-tumor response of the immune system. Not all
patients respond to anti-PD-1 or anti-PD-L1 treatment and therefore, combinations of
immunotherapy drugs have been investigated and proven more effective than single-agent
immunotherapy. These combinations, however, also increase the chance of immune toxicity.
Possible strategies to overcome this problem are to develop less toxic combinations of
immunotherapy drugs.
The T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) protein is also a
target for immunotherapy. TIGIT is overexpressed in several malignancies including,
melanoma, head and neck squamous cell carcinoma (HNSCC), and microsatellite instability
high (MSI-H) colorectal cancer. The combination of the anti-TIGIT drug tiragolumab with
the anti-PD-L1 drug atezolizumab increased the overall response rate by 15.1% compared to
atezolizumab alone in a study with non-small cell lung cancer patients (NSCLC), without
increasing toxicity.
In this trial, we will assess anti-tumor activity, safety, and tolerability of
atezolizumab in combination with tiragolumab in subjects with cancer. We will also
investigate proteins in the tumor to determine if we can predict which patients will
respond to the atezolizumab and tiragolumab treatment. Patients will be included in one
of four cohorts, namely: cohort 1, patients with localized HNSCC who will be treated with
atezolizumab and tiragolumab followed by tumor resection, cohort 2, patients with
metastatic MSI-H tumors, cohort 3, patients with irresectable or metastatic melanoma who
progressed after PD-1 treatment, or cohort 4, with patients with a locally advanced or
metastatic solid tumor for whom, based on available clinical data, treatment with
anti-PD-L1 immunotherapy may be beneficial. Acquired data could lead to improved, more
patient-tailored immune checkpoint inhibition.
Objective:
The main objective of the trial is to determine the pathological response rate in cohort
1 and the radiological response rates in cohort 2, 3 and 4. The secondary objectives of
the trial are the safety of atezolizumab and tiragolumab, the response rates measured by
overall response rate, disease free survival rate, duration of response and the last
secondary objective is to determine the correlation between the protein expression of
different proteins involved in the immune response of cancer to immunotherapy and the
different response rates as mentioned before.
Main trial endpoints:
Pathologic response of the primary tumor in patients with HNSCC and objective response
rate according to RECIST 1.1 and iRECIST in patients with advanced or metastatic MSI-H
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 trial endpoints:
The secondary endpoints are toxicity scored according to the common criteria for adverse
events version 5.0, disease free survival in patients with HNSCC, overall response rate,
progression free survival and duration of response in the patients in cohort 2, 3 and 4
as well as The correlation between the expression of the proteins TIGIT, PD-1, PD-L1 and
CD8 on tumor tissue and pathologic and radiographic response rate.
Trial design:
Open label phase 2 basket trial with atezolizumab and tiragolumab in patients with
localized HNSCC who will undergo surgery, and 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.
Trial population:
Subjects with localized HNSCC who will undergo surgery, and 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.
Interventions:
Subjects will receive atezolizumab and tiragolumab every 3-weeks until 1) resection as
scheduled for HNSCC after 2 courses, 2) resectable disease for the MSI-H tumors, 3)
progressive disease or side effects requiring treatment termination or 4) a maximum of 2
years. At baseline archival tissue or a tumor biopsy will be obtained and tissue will be
collected once during the trial and when lesions are surgically resected. Blood samples
will be collected during the trial to measure circulating tumor DNA. During the trial
regular CT or MRI scans will be made to monitor the response to the treatment.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Medical Center Groningen
Address:
City:
Groningen
Zip:
9713 GZ
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Derk-Jan de Groot, MD, PhD
Phone:
+31 50 361 6161
Email:
d.j.a.de.groot@umcg.nl
Contact backup:
Last name:
Daan Knapen, MD
Phone:
+31 50 361 6161
Email:
d.g.knapen@umcg.nl
Investigator:
Last name:
Derk-Jan de Groot, MD, PhD
Email:
Principal Investigator
Start date:
October 18, 2023
Completion date:
September 2027
Lead sponsor:
Agency:
University Medical Center Groningen
Agency class:
Other
Source:
University Medical Center Groningen
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05483400
