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

Safety

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

Time frame: From enrollment through study completion, approximately 48 months.

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).

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

Time frame: Predose and up to 24 hours postdose.

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

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

Time frame: Predose and up to 24 hours postdose.

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

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

Time frame: Predose and up to 24 hours postdose.

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

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

Time frame: Predose and up to 24 hours postdose.

Objective Response Rate (ORR)

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.

Time frame: 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).

Disease Control Rate (DCR)

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

Time frame: 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).

Clinical benefit Rate (CBR)

The CBR is defined as the percentage of subjects who achieve a CR, PR, or at least 12 weeks of SD as a result of therapy.

Time frame: 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).

Time to Tumor Response (TTR)

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.

Time frame: 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).

Duration of Response (DOR)

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.

Time frame: 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 ends or patient discontinue from the study, whichever occurs first (up to approximately 4 years).

Progression-free Survival (PFS)

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.

Time frame: 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).

Overall Survival

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

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

ERTC-QLC-C30

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 (in Phase 1 Part 2 and Phase 2).

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

NSCLC-SAQ

Change from Baseline in Patient Reported Outcome Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) at Treatment Cycle 2 and beyond (in Phase 1 Part 2 and Phase 2).

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