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

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)

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.

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.

Study Overview

• Status: Recruiting
• Conditions: NSCLC (Advanced Non-small Cell Lung Cancer)
• Intervention / Treatment: Drug: BH-30643

Detailed Description

BH-30643 is a novel, orally available, non-covalent, macrocyclic, mutant selective OMNI-EGFR inhibitor that targets a broad diversity of mutations in the EGFR kinase domain. These include EGFR classical mutations (e.g., ex19del and L858R) as well as less common (atypical) mutations (including G719X, S768I, L861Q, E709X, and beyond). BH-30643 also overcomes a variety of mutations which can cause resistance to previously approved EGFR TKIs (including both C797S and T790M). BH-30643 was designed to be selective over wildtype EGFR and HER2.

• Study Type: Interventional
• Enrollment (Estimated): 266
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sponsor Contact; Phone Number: (858) 732-3880; Email: clinicaltrials@bhtherapeutics.com

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Health
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G1Z2
      • Recruiting
      • Cross Cancer Insitute
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Princess Margaret Cancer Centre
• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital
  • New Territories
    • Shatin, New Territories, Hong Kong
      • Recruiting
      • Prince of Wales Hospital
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 227-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Osaka
    • Osakasayama-shi, Osaka, Japan
      • Recruiting
      • Kindai University Hospital
  • Tokyo
    • Tsukiji, Tokyo, Japan
      • Recruiting
      • National Cancer Center Hospital
• Malaysia
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Recruiting
      • Sarawak General Hosital
• Singapore
  • Kent Ridge, Singapore, 119074
    • Recruiting
    • National University Hospital
  • Singapore, Singapore, 168583
    • Recruiting
    • National Cancer Centre - Singapore
• South Korea
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 06351'
    • Recruiting
    • Samsung Medical Center
• Taiwan
  • Taichung, Taiwan, 407219
    • Recruiting
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Cancer Center
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic Hospital - Arizona
  • California
    • Irvine, California, United States, 92697
      • Recruiting
      • The Regents of the University of California - Irvine, CA Campus
    • La Jolla, California, United States, 92093
      • Recruiting
      • UC San Diego Moores Cancer Center
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California, Davis Comprehensive Cancer Center
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University - Cancer Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • Georgetown University Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic - Florida
    • Orlando, Florida, United States, 32827
      • Recruiting
      • Sarah Cancer Research Institution - Florida Cancer Specialist
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern Medicine - Northwestern Memorial Hospital Galter Pavilion
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02214
      • Recruiting
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Hospital - Rochester, MN
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • Recruiting
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University, Sidney Kimmel Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute, LLC
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas - M.D. Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Dose Escalation and Expansion; BH-30643 monotherapy for dose escalation; BH-30643 monotherapy for dose expansion/optimization at doses determined from dose escalation data; BH-30643 twice daily oral dosing	Drug: BH-30643; BH-30643 will be provided as either 10 mg or 40 mg capsules. Subjects will take BH-30643 orally depending on their dose level assignment.
Experimental: Phase 2; BH-30643 administered at the RP2D dose determined in Phase 1	Drug: BH-30643; BH-30643 will be provided as either 10 mg or 40 mg capsules. Subjects will take BH-30643 orally depending on their dose level assignment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicities (DLTs) (Phase 1, Dose Escalation)	Assess dose-limiting toxicities (DLTs) as defined in the study protocol.	Within the first 21 days of the first dose of BH-30643.
Recommended Phase 2 dose (RP2D) (Phase 1, Dose Expansion/Optimization)	Determine the RP2D for Phase 2.	Within 21 days of last participant dosed during Dose Expansion/Optimization.
Objective Response Rate (ORR) (Phase 2)	Determine ORR as assessed by Blinded Independent Central Review (BICR).	Approximately 3 years after the first participant dosed.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Assess incidence and severity of treatment-emergent adverse events (TEAEs), as defined by CTCAE, V5.0 (Phase 1 and Phase 2).	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.	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.	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.	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.	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.	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).	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.	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.	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.	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.	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.	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).	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).	From enrollment until the end of treatment, up till patient discontinue from treatment due to any reason (up to approximately 4 years).

Collaborators and Investigators

• Sponsor: BlossomHill Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2025
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): July 31, 2029

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; EGFR; Non-small Cell Lung Cancer; Tyrosine kinase inhibitor; TKI; EGFR mutation; T790M; Metastatic NSCLC; HER2 mutation; EGFR kinase domain mutations; G719X; S768I; E709X; L747X; Locally Advanced NSCLC; Ex19del; L858R; EGFR activating mutation; C797S; EGFR resistant mutation; EGFR classical mutation; EGFR atypical mutation; EGFR exon20 insertion; EGFR uncommon mutation; BH-30643; OMNI-EGFR; EGFR common mutation; EGFR del E746_A750; Exon 19 deletion; C797G; C797X; G724X; L718V; L718X; L861Q; S768X; Exon 19 insertion; L833X; L861X; V769X; V834X
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: BH-30643-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No