First-In-Human Study of STX-721/PFL-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR or HER2 Exon 20 Insertion Mutations

Key Inclusion Criteria:

1. Has histologically- or cytologically confirmed diagnosis of NSCLC Stage IIIB/C or IVnot eligible for curative intent surgery or chemoradiation

2. Part 1: Tumor tissue EGFR or HER2 exon 20 insertion mutations confirmed by qualifiedlocal laboratories. Parts 2 and 3: EGFR/HER2 exon 20 insertion mutations confirmedby qualified local laboratories

3. Part 1: Has received all approved therapies for advanced or metastatic NSCLC or isineligible. Part 2 and Part 3: Has received at least 1, but not more than 2, priorlines of approved treatment for advanced or metastatic NSCLC, 1 of which must beplatinum-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 archivaltumor 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 anyEGFR kinase domain activating mutation concurrent with either a T790M and/or C797Sresistance mutations

2. Has history (within ≤2 years before screening) of solid tumor or hematologicalmalignancy 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 baselinelevels or to CTCAE Grade ≤1, except for alopecia and peripheral neuropathy

5. Has any condition for which, in the opinion of the investigator, participation wouldnot be in the best interest of the participant (e.g., could compromise theparticipant's well-being) or would prevent, limit, or confound theprotocol-specified assessments