A Study of BH-30643 in Subjects With Locally Advanced or Metastatic NSCLC Harboring EGFR and/or HER2 Mutations

Dose-limiting toxicities (DLTs) (Phase 1, Dose Escalation)

Timeframe: Within the first 21 days of the first dose of BH-30643.

Assess dose-limiting toxicities (DLTs) as defined in the study protocol.

Recommended Phase 2 dose (RP2D) (Phase 1, Dose Expansion/Optimization)

Timeframe: Within 21 days of last participant dosed during Dose Expansion/Optimization.

Determine the RP2D for Phase 2.

Objective Response Rate (ORR) (Phase 2)

Timeframe: Approximately 3 years after the first participant dosed.

Determine ORR as assessed by Blinded Independent Central Review (BICR).

Safety

Timeframe: From enrollment through study completion, approximately 48 months.

Assess incidence and severity of treatment-emergent adverse events (TEAEs), as defined by CTCAE, V5.0 (Phase 1 and Phase 2).

Area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration (AUClast) of BH-30643 for Single dose (Phase 1).

Timeframe: Predose and up to 24 hours postdose.

Determine area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration (AUClast) of BH-30643.

Maximum observed plasma concentration (Cmax) of BH-30643 for Single dose (Phase 1).

Timeframe: Predose and up to 24 hours postdose.

Determine maximum observed plasma concentration (Cmax) of BH-30643.

Time to reach Cmax (Tmax) of BH-30643 for Single dose (Phase 1).

Timeframe: Predose and up to 24 hours postdose.

Determine time to reach Cmax (Tmax) of BH-30643.

Area under the plasma concentration-time curve at steady state (AUCss) of BH-30643 for multiple doses (Phase 1) at steady state.

Timeframe: Predose and up to 24 hours postdose.

Determine area under the plasma concentration-time curve at steady state (AUCss) of BH-30643.

Objective Response Rate (ORR)

Timeframe: From enrollment until the date of the first documented progression or death from any cause, whichever occurs first, assessed up to study ends or patient discontinue from the study, whichever occurs first (up to approximately 4 years).

The ORR is defined as a complete response (CR) or partial response (PR) per RECIST v1.1 recorded from first treatment until disease progression or start of new anti-cancer therapy. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met.

Disease Control Rate (DCR)

Timeframe: From enrollment until the date of the first documented progression or death from any cause, whichever occurs first, assessed up to study ends or patient discontinue from the study, whichever occurs first (up to approximately 4 years).

The DCR is defined as the percentage of subjects whose therapeutic intervention has led to a CR, PR, or stable disease (SD).

Time to Tumor Response (TTR)

Timeframe: From first dose to the first occurrence of response, assessed up to the date of first documented progression or death from any cause, whichever occurs first (up to approximately 4 years).

Time to tumor response (TTR) is defined for subjects with a confirmed objective response, as the time from the date of first treatment to the first documentation of objective response (CR or PR) which is subsequently confirmed.

Duration of Response (DOR)

Timeframe: From first occurrence of response until the date of the first documented progression or death from any cause, whichever occurs first, assessed up to study end or patient discontinuation from the study, whichever occurs first (up to approximately 4 years)

The DOR is defined, for subjects with an objective response per RECIST v1.1, as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.

Progression-free Survival (PFS)

Timeframe: From enrollment until the date of the first documented progression or death from any cause, whichever occurs first, assessed up to study end or patient discontinuation from the study, whichever occurs first (up to approximately 4 years).

The endpoint PFS is defined as the time from the date of the first treatment to the date of the first documentation of objective progression of disease or death due to any cause, whichever occurs first.

Overall Survival

Timeframe: From enrollment until the date of death from any cause, assessed up to study end or patient discontinuation from the study, whichever occurs first (up to approximately 4 years).

Overall survival is defined as the time from the date of first treatment to the date of death due to any cause.

ERTC-QLC-C30

Timeframe: From enrollment until the end of treatment, up till patient discontinue from treatment due to any reason (up to approximately 4 years).

Change from Baseline in Patient Reported Outcome European Organization for Research and Treatment Quality of Life Questionnaire (ERTC-QLC-C30) at Treatment Cycle 2 and beyond (Phase 2).

NSCLC-SAQ

Timeframe: From enrollment until the end of treatment, up till patient discontinues treatment for any reason (up to approximately 4 years).

Change from Baseline in Patient Reported Outcome Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) at Treatment Cycle 2 and beyond (Phase 2).