First-In-Human Study of STX-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations

Study Overview
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Brief Summary
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Study STX-721-101 is an open label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of STX-721 in participants with non-small cell lung cancer (NSCLC) carrying EGFR/HER2 exon 20 insertion (ex20ins) mutations.

Official Title
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First-In-Human Study of STX-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations

Conditions
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Non-Small Cell Lung Cancer, NSCLC, EGFR/HER2 Exon 20 Insertion Mutation

Intervention / Treatment
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* Drug: STX-721 (Escalated)
* Drug: STX-721 (2 doses)
* Drug: STX-721 (RP2D)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Has histologically- or cytologically confirmed diagnosis of NSCLC Stage IIIB/C or IV not eligible for curative intent surgery or chemoradiation. Tumor tissue EGFR exon 20 insertion mutations confirmed by qualified local laboratories. Has new or recent tumor biopsy (collected at screening, if feasible) or archival tumor specimen collected in the past 10 years available for genomic profiling (see lab manual for minimum tissue requirements). Is ≥18 years of age at the time of signing the ICF. Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Key Exclusion Criteria: Has a tumor that is known to harbor concurrent T790M and C797S resistance mutations. Has history (within ≤2 years before screening) of solid tumor or hematological malignancy that is histologically distinct from NSCLC. Has symptomatic brain or spinal metastases. Has toxicities from previous anticancer therapies that have not resolved to baseline levels or to CTCAE Grade ≤1, except for alopecia and peripheral neuropathy. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., could compromise the participant's well-being) or would prevent, limit, or confound the protocol-specified assessments.

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: Part 1: Dose Escalation<br> | Drug: STX-721 (Escalated)<br>* STX-721 dose will be escalated per Safety Evaluation Team (SET) decision and BLRM-design.<br>|
| Experimental: Part 2: RP2D Selection<br> | Drug: STX-721 (2 doses)<br>* Participants will receive 2 doses of STX-721.<br>|
| Experimental: Part 3: Dose Expansion<br> | Drug: STX-721 (RP2D)<br>* Participants will receive the RP2D of STX-721.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 Dose Escalation (MTD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment |  | 28 days | 
| Part 1 Dose Escalation (OBD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment |  | 28 days | 
| Part 2 RP2D Selection: C(max) of STX-721 |  | 1 year | 
| Part 2 RP2D Selection: AUC(0-inf) of STX-721 |  | 1 year | 
| Part 2 RP2D Selection: AUC(0-t) of STX-721 |  | 1 year | 
| Part 2 RP2D Selection: AUC(0-τ) of STX-721 |  | 1 year | 
| Part 2 RP2D Selection: Change from baseline in circulating tumor DNA (ctDNA) analysis of EGFR mutations |  | 1 year | 
| Part 2 RP2D Selection: Change from baseline in EGFR signaling |  | 1 year | 
| Part 2 RP2D Selection: Change in absolute value versus time in circulating tumor DNA (ctDNA) analysis of EGFR mutations |  | 1 year | 
| Part 2 RP2D Selection: Change in absolute value versus time in EGFR signaling |  | 1 year | 
| Part 2 RP2D Selection: Number of participants with confirmed objective response rate (ORR) defined as the percentage of participants with partial response (PR) or complete response (CR) based on RECIST v1.1 per investigator assessment. |  | 1 year | 
| Part 3 Dose Expansion: Number of participants with confirmed ORR defined as the percentage of participants with PR or complete response CR based on RECIST v1.1 per investigator assessment. |  | 1 year |