THIO Sequenced With Cemiplimab in Advanced NSCLC

Description

The current Phase 2, open-label, multicenter study, comprised of 3 parts, is designed to evaluate the safety and efficacy of THIO sequenced with cemiplimab in subjects with advanced NSCLC. This study could establish THIO followed by cemiplimab as a potential treatment regimen in a high unmet medical need setting.

The study evaluates the safety and efficacy of different doses of THIO sequenced with fixed-dose of cemiplimab (collectively called investigational product [IP]) in subjects with advanced NSCLC who progressed or relapsed after receiving first line therapy which included ICI.

This study will be a Phase 2, open-label, multicenter study comprised of 3 parts:

• Part A -Safety lead-in, modified 3+3 design
• Part B - Simon's 2-stage design, randomized, dose-finding, 3-arm (or 2 arm, based on Part A emerging data)
• Part C (optional) - high dose arm, 3+3 design followed by Simon's 2-stage design if cohort expansion occurs

A Safety Review Committee (SRC) will monitor subject safety during the study and will make recommendations to the Sponsor regarding enrollment, eg, de-escalating dose in Part A, proceeding to Part B, expanding an arm in Part B and opening Part C (optional) of the study based on emerging data from prior study parts.

In each study part, on Cycle 1, Day 1, eligible subjects will initiate treatment with THIO (doses will be as described for each study part below) as intravenous (IV) infusion on Days 1-3 of every 3 week cycle (Q3W) followed by a fixed-dose of cemiplimab (350 mg IV) on Day 5 Q3W. Subjects may continue dosing with THIO followed by cemiplimab Q3W until disease progression or occurrence of an unacceptable toxicity, withdrawal of consent, death, or one year on treatment.

The initial radiographic imaging for baseline assessment will be conducted by the investigator within 28 days of the first dose of THIO (if not performed in the 4-6 weeks prior to screening) for tumor evaluation and measurements. The on-treatment radiographic assessments will be performed initially at 6 weeks intervals (ie. Cycle 3, Day 1 and Cycle 5, Day 1) and repeated thereafter every 9-12 weeks ± 7 days as clinically indicated. The radiographic scans will be assessed by the investigator according to RECIST v1.1 and/or immune RECIST (iRECIST) until disease progression, or until initiation of a new anticancer treatment (whichever occurs first). Confirmation of CR, PR, stable disease (SD),and PD by a consecutive radiographic imaging (computed tomography/magnetic resonance imaging; same modality to be used for a given subject throughout the study) assessment at least 4 weeks from the date of first documentation will be required. Radiographic scans will be collected and held for possible future retrospective independent evaluation. To account for tumor pseudoprogression or delayed response with anti-PD-1/PD-L1 immunotherapies, subjects may continue to receive IP beyond RECIST v1.1 defined progression at the discretion of the Investigator and be assessed at a subsequent tumor assessment time point (≥ 4 weeks later but not exceeding 6 to 8 weeks from the date of initial documentation of disease progression) to confirm disease progression according to iRECIST. Subjects must be consented to receive the IP beyond the initial progression and will discontinue IP once the progression is confirmed.

All subjects will undergo end of treatment (EoT) visit 30 days post last treatment with IP. Subjects will have follow-up visits every 6 weeks for approximately 6 months and then at 9 months and 12 months after the last dose of IP or until they start a new anticancer therapy, whichever is earlier. In subjects who discontinued IP due to toxicity, radiographic imaging will be done every 3 months until disease progression or until the subject initiates another anti-cancer therapy.

In each study part, for each subject, the study is expected to last as follows:

Screening period: Up to 28 days

Treatment period: Until disease progression assessed by the Investigator per RECIST v1.1 and/or iRECIST or occurrence of an unacceptable toxicity, withdrawal of consent, unacceptable toxicity, disease progression, death, or one year on treatment

Short-term Follow- up: Up to 30 days after the last dose of THIO

Long-term Follow-up: Up to a maximum of 12 months after the last dose of IP of the last subject or earlier if the study is terminated by the Sponsor

The Safety Review Committee (SRC) will be comprised of Sponsor's Medical Monitor (or designee), safety physician, statistician and a subset of investigators. The SRC will meet regularly to review the safety information of each study part and make recommendation to the Sponsor.

The Sponsor has carefully considered potential risks, uncertainties, and antitumor benefits that may be associated with THIO + cemiplimab for the treatment of advanced NSCLC.

The potential risks have been taken into consideration in the design and safety monitoring of this study to mitigate any risk. The study safety measures comprise of specific inclusion/exclusion criteria for participation in the study. This study also includes the medical management of potential toxicities as well as guidance on investigational product (IP) dosing, interruption or discontinuation.

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