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

Scorpion Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: STX-721 (2 doses); Drug: STX-721 (Escalated); Drug: STX-721 (RP2D)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06043817

STX-721-101

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Has histologically- or cytologically confirmed diagnosis of NSCLC Stage IIIB/C or IV not eligible for curative intent surgery or chemoradiation
2. Part 1: Tumor tissue EGFR or HER2 exon 20 insertion mutations confirmed by qualified local laboratories. Parts 2 and 3: EGFR exon 20 insertion mutations confirmed by qualified local laboratories
3. Part 1: Has received all approved therapies for advanced or metastatic NSCLC or is ineligible. Part 2 and Part 3: Has received at least 1, but not more than 2, prior lines of treatment for advanced or metastatic NSCLC, 1 of which must be platinum-based chemotherapy unless contraindicated
4. Has documented tumor progression (based on radiological imaging)
5. 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
6. Has at least one measurable tumor lesion per RECIST v1.1
7. Is ≥18 years of age at the time of signing the ICF
8. Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Key Exclusion Criteria:

1. Has a tumor that is known to harbor EGFR ex20ins p.H773_V774insH variant, or any EGFR kinase domain activating mutation concurrent with either a T790M and/or C797S resistance mutations
2. Has history (within ≤2 years before screening) of solid tumor or hematological malignancy that is histologically distinct from NSCLC
3. Has symptomatic brain or spinal metastases
4. Has toxicities from previous anticancer therapies that have not resolved to baseline levels or to CTCAE Grade ≤1, except for alopecia and peripheral neuropathy
5. 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

120 participants in 3 patient groups

Part 1: Dose Escalation

Experimental group

Treatment:

Drug: STX-721 (Escalated)

Part 2: RP2D Selection

Experimental group

Treatment:

Drug: STX-721 (2 doses)

Part 3: Dose Expansion

Experimental group

Treatment:

Drug: STX-721 (RP2D)