A Multicenter, Open-Label, Dose-Finding, Phase 2 Study Evaluating THIO Sequenced with Cemiplimab (LIBTAYO®) in Subjects with Advanced Non-Small Cell Lung Cancer (NSCLC)

Phase 1

• Conditions: on-Small Cell Lung Cancer; MedDRA version: 21.1Level: PTClassification code: 10029519Term: Non-small cell lung cancer stage III Class: 100000004864; MedDRA version: 21.1Level: PTClassification code: 10061873Term: Non-small cell lung cancer Class: 100000004864; MedDRA version: 21.1Level: PTClassification code: 10029522Term: Non-small cell lung cancer stage IV Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-504595-26-00
• Lead Sponsor: Maia Biotechnology Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-30
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

At least 18 years of age at the time of signing the Informed Consent Form (ICF) prior to initiation of any study specific activities/procedures., WOCBP must agree to use a highly effective birth control and refrain from oocyte donation during the study (prior to the first dose with THIO, for the duration of the treatment with THIO plus 6 months after last dose of IP), if conception is possible during this interval., Male subjects and WOCBP partners of male subjects should use a combination of the methods specified in Section 10.4 for the women along with a male condom from first dose of THIO (Cycle 1, Day 1), for the duration of the treatment with THIO plus 6 months after last dose of IP, unless permanently sterile by bilateral orchidectomy. Male subjects should also refrain from sperm donation during this time., Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol., Stage 3 or 4 histologically or cytologically confirmed NSCLC which has progressed or relapsed after treatment in the advanced setting ? Stage 4 subjects – must have progressed or relapsed after first line treatment. ? Stage 3 subjects – must have already failed, or be ineligible for, local, curative-intent therapy including surgery, and/or chemoradiation. Stage 3 subjects with documented relapse/progression after consolidation therapy with durvalumab following definitive chemoradiotherapy are eligible. ? Patients with primary resistance, as defined by the Society for Immunotherapy of Cancer (SITC) immunotherapy resistance task force (Kluger, 2020), are excluded: ? Subjects with drug exposure > 6 weeks who achieved a PR or CR then progressed before 6 months, would still be eligible., Only one prior treatment for NSCLC in the advanced setting, which must have included one anti-PD-1/PD-L1 agent with documented radiographic disease progression on or after treatment. ? Prior treatment may have been with anti-PD-1/PD-L1 agent either alone or in combination with a non-anti-PD-1/PD-L1 treatment (e.g., chemotherapy) ? Prior platinum-based chemotherapy is not required for eligibility. ? Subjects receiving more than one ICI in the advanced setting (e.g., anti-PD-1/PD-L1 and anti-CTLA-4 compounds) will not be eligible., At least one measurable target lesion that meets the definition of RECIST v1.1., An archival tissue sample (FFPE tissue block or unstained slides) is required if tissue is available at baseline. Sample does not need to be received by central lab prior to C1D1. Subjects without archival tissue available at baseline may be eligible with Medical Monitor approval., Eastern Cooperative Oncology Group (ECOG) performance status of 0-1., Demonstrate adequate organ function as defined below. All screening laboratories should be performed up to 14 days before initiating IP: Bone marrow function: ? Neutrophil count = 1500/mm3, hemoglobin = 9.0 g/dL, platelet count = 100,000/mm3 Liver function: ? Total bilirubin = 1.5 x the upper limit of normal (ULN), up to = 3 × ULN due to Gilbert’s syndrome ? Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 1.5 × ULN. For subjects with liver metastases present at baseline, ALT and/or AST = 3 × ULN is permitted. Renal function: ? Creatinine clearance = 60 mL/min calculated by the Cockcroft-Gault formula using actual body weight (see Table 15) or 24-hour urine collection., Women of childbearing potential (WOCBP) must have negative seru

Exclusion Criteria

Have not recovered from adverse events (must be Grade f 1) due to prior anti-cancer treatment., Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions: ? Controlled type 1 diabetes; ? Hypothyroidism (provided it is managed with hormone replacement therapy only); ? Controlled celiac disease; ? Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia); ? Any other disease that is not expected to recur in the absence of external triggering factors., Pregnancy or lactating., A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the investigator and/or the Sponsor., Any other condition that, in the opinion of the investigator, would prohibit the subject from participating in the study., Prior chemotherapy and/or non-biologic targeted therapy within 4 weeks, or biologic targeted therapy, immunotherapy, and/or radiation therapy within 6 weeks prior to Cycle 1 Day 1. Subjects who receive targeted radiation therapy for localized palliative care may be eligible to start treatment < 6 weeks with Medical Monitor agreement., Prior treatment with cemiplimab., Undergone major surgery within 4 weeks prior to Cycle 1, Day 1., Received blood, red blood cell or platelet transfusion within 2 weeks before the first dose of IP., Any live, attenuated, inactivated or research vaccines within 30 days prior to the first dose of IP. Refer to Section 6.9.1 for prohibited vaccines. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed., Prior allogeneic hematopoietic stem cell transplant or solid organ transplant., Untreated or symptomatic central nervous system (CNS) metastases. Note: subjects with treated asymptomatic brain metastasis are eligible., Currently enrolled in a clinical study involving another IP or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study., History of allergy to excipients of THIO or cemiplimab., Active gastrointestinal bleeding as evidenced by either hematemesis or melena., History of another concurrent malignancy other than the present condition (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years., A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, adrenal replacement doses 10 mg daily prednisone equivalents, and systemic corticosteroids to manage adverse events (AEs) are permitted in the absence of active autoimmune disease., Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 2 weeks of screening., Positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active hepatitis B or hepatitis C., Significant cardiovascular impairment (history of New York Heart Association Functional Classification System Class III or IV) or a history of myocardial infarction or unstable angina within the past 6 months prior to IP initiation. a) QTcF > 480 msec at screening (based on average of triplicate ECGs at baseline). i. If the QTc is prolonged in a subject with a pac

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 1. To determine the safety and tolerability of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC.<br>2. To assess the efficacy of THIO administered in sequence with cemiplimab in subjects with advanced NSCLC.;Secondary Objective: Additional efficacy evaluation.;Primary end point(s): Incidence of dose limiting toxicities (DLTs; applicable for Part A and Part C), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) overall, by severity, by relationship to THIO, and those that led to discontinuation of THIO and/or withdrawal from study., ORR defined as the proportion of subjects with best overall confirmed response of either a complete response (CR) or partial response (PR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1., Disease control rate (DCR) defined as CR, PR or stable disease (SD) as assessed by the investigator based on RECIST v1.1.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):DoR;Secondary end point(s):PFS;Secondary end point(s):OS