Tislelizumab in Combination With Chemotherapy in First-line Treatment of Unresectable/Metastatic Non-small Cell Lung Cancer or Recurrent/Metastatic Squamous Cell Head and Neck Cancer

Phase 2

• Conditions: Health Condition 1: C760- Malignant neoplasm of head, face and neckHealth Condition 2: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung

• Registration Number: CTRI/2024/03/063500
• Lead Sponsor: B HEALTH TECHNOLOGIES PRIVATE LIMITED

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

1) Patient must sign a written ICF and understand and agree to comply with the requirements of the study and the schedule of assessments.

2) Age greater than or equals to 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place)

3) Cohort 1: NSCLC

a) Locally advanced or recurrent NSCLC that is not eligible for curative surgery and or definitive radiotherapy with or without chemoradiotherapy, or metastatic nonsquamous or squamous NSCLC.

b) No prior systemic treatment for metastatic NSCLC. Patients who have received prior neoadjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for nonmetastatic disease must have experienced a disease-free interval of = 6 months from the last dose of chemotherapy and or radiotherapy prior to signing informed consent.

c) No known mutations in:

(a)EGFR-sensitizing gene (e.g., exon 19 deletion or exon 21 L858R)

(b)ALK fusion oncogene

(c)Or other mutation routinely tested for at the discretion of the investigator and for which an approved targeted therapy exists.

Note: Non-squamous NSCLC patients with unknown EGFR and ALK mutational status, will be required to have tissue-based EGFR and ALK testing prior to enrollment. Squamous NSCLC patient with unknown EGFR and ALK mutational status will not be required to undergo testing prior to enrollment.

Cohort 2: HNSCC

a) Recurrent or metastatic HNSCC that is not amenable to by local curative therapies with surgery or radiation

b) Primary tumor site of oral cavity, oropharynx, hypopharynx, or larynx. Patients with a primary tumor site of nasopharynx are excluded (Note: human papillomavirus (HPV) status will not be required prior to entering the study).

c) No prior systemic therapy administered in recurrent or metastatic setting. Systemic therapy which was given as part of multimodal treatment for locally advanced disease is allowed.

d) Tumor progression or recurrence = 6 months after last dose of platinum therapy for patients who received multimodality treatment for locally advanced or locally recurrent disease.

4. All patients must provide archival tissue (formalin-fixed paraffin-embedded block containing tumor) that is collected less than 1 year prior to screening or a fresh biopsy (if archival tissue is not available). Specimens from metastatic bone lesions are not acceptable.

5. ECOG Performance Status less than equal to 1

6. Adequate organ function as indicated by the following laboratory values during screening:

a. Patients must not have required blood transfusion or growth factor support less than equal to 14 days before sample collection at screening for the following:

i. Absolute neutrophil count (ANC) greater than equal to 1.5 x 109 per L

ii. Platelets greater than equal to 100 x 109 per L

iii. Hemoglobin greater than equal to 90 g per L

b. Serum creatinine less than equal to 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate greater than equals to 45 mL min 1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation (Appendix 8)

c. Serum total bilirubin less than equal to 1.5 times the ULN (total bilirubin must be less than 3 times ULN for patients with Gilbert syndrome)

d. AST and ALT less than equal to 2.5 times the ULN or less 5 times the ULN if hepat

Exclusion Criteria

1. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.

2. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible.

3. Active leptomeningeal disease or uncontrolled, brain metastasis.

a. Patients with known untreated asymptomatic brain metastases (no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesion greater 1 by 5 cm) may participate but will require regular imaging of the brain as a site of disease.

b. Patients with a history of treated and, at the time of screening, stable central nervous system (CNS) metastases are eligible, provided that they meet all the following:

i. Brain imaging at screening shows no evidence of interim progression, patient is clinically stable for at least 2 weeks and without evidence of new brain metastases.

ii. Measurable and or evaluable disease outside the CNS.

iii. No ongoing requirement for corticosteroids as therapy for CNS disease; off steroids 14 days before enrollment; anticonvulsants at a stable dose are allowed.

iv. No stereotactic radiation or whole-brain radiation within 14 days before enrollment.

4. Active autoimmune diseases or history of autoimmune diseases that may relapse.

Note: Patients with the following diseases are not excluded and may proceed to further screening:

a. Controlled Type 1 diabetes

b. Hypothyroidism (provided that it is managed with hormone replacement therapy only)

c. Celiac disease controlled by diet alone.

d. Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia)

e. Any other disease that is not expected to recur in the absence of external triggering factors.

5. Any active malignancy less than equal to 2 years before the first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has previously been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, localized prostate cancer, carcinoma in situ of the cervix or breast).

6. Any condition that required systemic treatment with either corticosteroids (greater than 10 mg daily of prednisone or equivalent) or other immunosuppressive medication less than equal to 14 days before the first dose of study drug

Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded:

a. Adrenal replacement steroid (dose less than equal to 10 mg daily of prednisone or equivalent)

b. Topical, ocular, intra articular, intranasal, or inhaled corticosteroid with minimal systemic absorption

c. Short course (less than equal to 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a nonautoimmune condition (eg, delayed type hypersensitivity reaction caused by contact allergen

7. Uncontrolled diabetes or greater than Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or greater than equal to Grade 3 hypoalbuminemia less than equal to 14 days before the first dose of study drug.

8. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring freq

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the safety and tolerability profile of tislelizumab in combination with chemotherapy (comparator agents)Timepoint: The incidence and severity of AEs Will be assessed every 3 weeks during the entire course of the study.