Study to Evaluate D-1553 in Subjects With Lung Cancer

Study Overview
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Brief Summary
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This is a phase 1/2, open label study of D-1553 single agent treatment to assess the safety and tolerability, identify the MTD and RP2D, evaluate the PK properties and antitumor activities in subjects with advanced or metastatic NSCLC with KRasG12C mutation

Official Title
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A Phase 1/2, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of D-1553 in Subjects With Advanced or Metastatic Solid Tumors

Conditions
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NSCLC

Intervention / Treatment
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* Drug: D-1553


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with histologically proven, locally advanced, unresectable and/or metastatic NSCLC for which no standard treatment is available or the subject is refractory to or intolerant of existing standard treatment. 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 central laboratory. Subject has measurable disease according to RECIST, v1.1 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 1a Dose escalation of D-1553<br>Phase 1a will evaluate up to sequential cohorts with different doses of D-1553 to determine safety, tolerability, MTD and RDE in patients with solid tumors with KRasG12C mutation | 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>|
| Experimental: Phase 1b Dose expansion of D-1553<br>Phase 1b will evaluate more subjects with up to 2 different doses of D-1553 to confirm the recommended phase 2 dose. | 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>|
| Experimental: Phase 2 of D-1553 monotherapy<br>Phase 1b will evaluate more subjects at the recommended phase 2 dose of D-1553 to evaluate the efficacy. | 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>|

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 | Through 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]) | Through study completion, approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of D-1553 | Plasma concentration of D-1553 as a single agent in subjects with advanced or metastatic NSCLC with KRas G12C mutation | approximately 6 months |