A Study to Evaluate D-1553 in Combination Therapy in Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of D-1553 Combination Therapy in Subjects with KRAS G12C-mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer.

Official Title
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A Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of D-1553 Combination Therapy in Subjects With KRAS G12C-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Conditions
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NSCLC

Intervention / Treatment
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* Drug: D-1553
* Drug: Other


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with histologically proven, locally advanced or metastatic NSCLC for which has no standard treatment or the subject has been previously treated with first- or second-line systemic therapy. Subject has KRasG12C mutation in tumor tissue or other biospecimens containing cancer cells or DNA. Historical, local laboratory result (up to 5 years prior to this study) can be used for Phase 1 subjects. Phase 2 subjects must be tested for KRasG12C mutation by a local laboratory. Subject has measurable disease according to RECIST v1.1. For phase 1b subjects who have no measurable lesions but whose disease can be evaluated are also acceptable. Exclusion Criteria: Subject with unstable or progressive central nervous system (CNS) metastases. Subjects with clinically significant cardiovascular disease. Subject with interstitial lung disease (ILD) or any active systemic infection including but not limited to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Subject has impaired gastrointestinal (GI) function or GI diseases that may significantly alter the absorption or metabolism of oral medications. Subject is pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1b Dose escalation of D-1553 combination therapies<br>Phase 1b will determine maximal tolerated dose and/or recommended phase 2 dose of D-1553 in combination with immunotherapy or targeted therapy in patients with KRAS G12C-mutated locally advanced or metastatic NSCLC. | Drug: D-1553<br>* D-1553 is a novel, targeted KRasG12C inhibitor that is being developed as a potential oral agent for advanced or metastatic solid tumors with KRasG12C mutation.<br>Drug: Other<br>* Standard treatment of NSCLC.<br>|
| Experimental: Phase 2 of D-1553 combination therapies<br>Phase 2 will evaluate the efficacy and safety of D-1553 combined with immunotherapy or targeted therapy in patients with KRAS G12C-mutated locally advanced or metastatic NSCLC. | Drug: D-1553<br>* D-1553 is a novel, targeted KRasG12C inhibitor that is being developed as a potential oral agent for advanced or metastatic solid tumors with KRasG12C mutation.<br>Drug: Other<br>* Standard treatment of NSCLC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject incidence of Dose-limiting toxicities (DLT) | Subject incidence of Dose-limiting toxicities (DLT) | Through out the DLT period, approximately 21 days | 
| Number of subjects participants with adverse events | Number of subjects participants with adverse events | Till study completion, approximately 3 years | 
| Antitumor activity of D-1553 in subjects with advanced or metastatic NSCLC with KRASG12C mutation | Overall Response Rate (ORR, Complete Response [CR] + Partial Response [PR]) | Till study completion, approximately 3 years |