Clinical trial NCT06706076: A Study of BH-30643 in Subjects With Locally Advanced or Metastatic NSCLC Harboring EGFR and/or HER2 Mutations
Official title: A Phase 1/2 Open-Label, Multicenter, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of BH-30643 in Adult Subjects With Locally Advanced or Metastatic NSCLC Harboring EGFR and/or HER2 Mutations (SOLARA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: NSCLC (Advanced Non-small Cell Lung Cancer)
Keywords: NSCLC
Locally Advanced NSCLC
Metastatic NSCLC
Non-small Cell Lung Cancer
HER2 mutation
EGFR mutation
EGFR classical mutation
EGFR atypical mutation
EGFR exon20 insertion
EGFR uncommon mutation
EGFR resistant mutation
Lead sponsor: BlossomHill Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-11-26
Enrollment: 266
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: BH-30643-01 is a Phase 1/2, first-in-human, open label, dose escalation and expansion study in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and/or human epidermal growth factor receptor (HER2) mutations. The study drug, BH-30643 capsules, will be self-administered by mouth twice daily in 21-day cycles.

Phase 1 will determine the recommended Phase 2 dose (RP2D) and, if applicable, the maximum tolerated dose (MTD) of BH-30643.

Phase 2 will further evaluate the antitumor efficacy and safety in specified cohorts determined by EGFR/HER2 mutation subtypes and/or treatment history at the RP2D, as well as the population PK.

Detailed description: BH-30643 is a novel, orally available, reversible, mutant selective, macrocyclic OMNI-EGFR inhibitor that targets mutations in the EGFR kinase domain, including EGFR classical, atypical (also called uncommon or nonclassical), and ex20ins mutations, and a variety of EGFR resistant mutations (eg, ex19del/T790M, ex19del/C797S, ex19del/T790M/C797S, L858R/T790M, L858R/C797S, and L858R/T790M/C797S), as well as HER2 mutations including ex20ins mutations. In addition, BH-30643 has demonstrated good selectivity over wildtype EGFR and HER2. This Phase1/2, open label, multicenter study will assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary anti-tumor activity of BH-30643 in patients with NSCLC having EGFR and/or HER2 mutations.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 years or legal adult.
* Pathologically confirmed diagnosis of locally advanced or metastatic NSCLC with EGFR (classical, atypical, exon20 insertion) or HER2 mutations in the kinase domain of exons 18, 19, 20, or 21. EGFR mutations include activating and acquired EGFR resistance mutations that might form compound mutations.
* Had received standard therapies.
* Has at least 1 measurable target extracranial lesion according to RECIST v1.1.
* Eastern Cooperative Oncology Group Performance Status ≤ 1.
* Has a life expectancy of ≥ 3 months.
* Has adequate hematologic, hepatic, and renal function. \*The above are a summary; other Inclusion Criteria details may apply.

Exclusion Criteria:

* History of any concurrent malignancy within the previous 2 years.
* Known other oncogenic driver alterations (eg, moderate or high MET amplification) or histological transformation (eg, to small cell carcinoma, etc.).
* Unresolved toxicities from prior therapies.
* Any significant and uncontrolled medical condition, such as infection.
* History of interstitial lung disease from any cause
* Clinically significant cardiovascular event within 6 months or significant history of major organ.
* Actively receiving investigational therapy(ies) in another clinical study. \*The above are a summary; other Exclusion Criteria details may apply.

Primary outcomes:
measure: Dose-limiting toxicities (DLTs) (Phase 1, Dose Escalation)
timeFrame: Within the first 21 days of the first dose of BH-30643.
measure: Recommended Phase 2 dose (RP2D) (Phase 1, Dose Expansion/Optimization)
timeFrame: Within 21 days of last participant dosed during Dose Expansion/Optimization.
measure: Objective Response Rate (ORR) (Phase 2)
timeFrame: Approximately 3 years after the first participant dosed.
Secondary outcomes:
measure: Safety
timeFrame: From enrollment through study completion, approximately 48 months.
measure: 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.
measure: Maximum observed plasma concentration (Cmax) of BH-30643 for Single dose (Phase 1).
timeFrame: Predose and up to 24 hours postdose.
measure: Time to reach Cmax (Tmax) of BH-30643 for Single dose (Phase 1).
timeFrame: Predose and up to 24 hours postdose.
measure: 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.
measure: 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).
measure: 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).
measure: Clinical benefit Rate (CBR)
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).
measure: 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).
measure: 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 ends or patient discontinue from the study, whichever occurs first (up to approximately 4 years).
measure: 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 ends or patient discontinue from the study, whichever occurs first (up to approximately 4 years).
measure: Overall Survival
timeFrame: 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).
measure: 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).
measure: NSCLC-SAQ
timeFrame: From enrollment until the end of treatment, up till patient discontinue from treatment due to any reason (up to approximately 4 years).
Other outcomes:
Locations:
city: Irvine
country: United States
facility: The Regents of the University of California - Irvine, CA Campus
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center
state: California
city: Lake Mary
country: United States
facility: Sarah Cancer Research Institution - Florida Cancer Specialist
state: Florida
city: Chicago
country: United States
facility: Northwestern Medicine - Northwestern Memorial Hospital Galter Pavilion
state: Illinois
city: Nashville
country: United States
facility: Sarah Cannon Research Institute, LLC
state: Tennessee
city: Houston
country: United States
facility: The University of Texas - M.D. Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Tsukiji
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
Study officials:
References: