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)

Overview

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, both as a monotherapy and in combination with chemotherapy. 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, 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.

Interventions

• Drug BH-30643
  BH-30643 will be provided as either 10 mg or 40 mg capsules or tablets. Subjects will take BH-30643 orally depending on their dose level assignment.
• Drug BH-30643 combo therapy with Carboplatin/Pemetrexed
  BH-30643 will be provided as either 10 mg or 40 mg capsules or tablets in combo therapy with Carboplatin/Pemetrexed. Subjects will take BH-30643 orally depending on their dose level assignment. Carboplatin/Pemetrexed will be administered according to standard of care
• 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

Primary outcome measures

• Dose-limiting toxicities (DLTs) (Phase 1, Dose Escalation) [Time frame: Within the first 21 days of the first dose of BH-30643.]
• Recommended Phase 2 dose (RP2D) (Phase 1, Dose Expansion/Optimization) [Time frame: Within 21 days of last participant dosed during Dose Expansion/Optimization.]
• Objective Response Rate (ORR) (Phase 2) [Time frame: Approximately 3 years after the first participant dosed.]

Secondary outcome measures (12)

• Safety [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). [Time frame: Predose and up to 24 hours postdose.]
• Maximum observed plasma concentration (Cmax) of BH-30643 for Single dose (Phase 1). [Time frame: Predose and up to 24 hours postdose.]
• Time to reach Cmax (Tmax) of BH-30643 for Single dose (Phase 1). [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. [Time frame: Predose and up to 24 hours postdose.]
• Objective Response Rate (ORR) [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) [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 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) [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 end or patient discontinuation from the study, whichever occurs first (up to approximately 4 years)]
• Progression-free Survival (PFS) [Time frame: 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).]
• Overall Survival [Time frame: 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).]
• ERTC-QLC-C30 [Time frame: From enrollment until the end of treatment, up till patient discontinue from treatment due to any reason (up to approximately 4 years).]

Eligibility criteria

Inclusion criteria

• ≥ 18 years or legal adult.
• Pathologically confirmed diagnosis of locally advanced or metastatic NSCLC with EGFR or HER2 mutations in the kinase domain of exons 18, 19, 20, or 21.
• 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.
• Active or history of interstitial lung disease from any cause
• Clinically significant cardiovascular event within 6 months or significant history of major organ.

• The above are a summary; other Exclusion Criteria details may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 24 centers

• Mayo Clinic Hospital - Arizona — Phoenix
• The Regents of the University of California - Irvine, CA Campus — Irvine
• UC San Diego Moores Cancer Center — La Jolla
• University of California, Davis Comprehensive Cancer Center — Sacramento
• Stanford University Medical Center — Stanford
• Yale University - Cancer Center — New Haven
• Georgetown University Medical Center — Washington D.C.
• Mayo Clinic - Florida — Jacksonville
• … and 16 more centers

Japan · 3 centers

• National Cancer Center Hospital East — Kashiwa
• Kindai University Hospital — Osakasayama-shi
• National Cancer Center Hospital — Tsukiji

South Korea · 3 centers

• Seoul National University Hospital — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

Taiwan · 3 centers

• Taichung Veterans General Hospital — Taichung
• National Taiwan University Cancer Center — Taipei
• National Taiwan University Hospital — Taipei

Australia · 2 centers

• Austin Health — Heidelberg
• Peter MacCallum Cancer Centre — Melbourne

Canada · 2 centers

• Cross Cancer Institute — Edmonton
• Princess Margaret Cancer Centre — Toronto

Hong Kong · 2 centers

• Prince of Wales Hospital — Shatin
• Queen Mary Hospital — Hong Kong

Singapore · 2 centers

• National University Hospital — Kent Ridge
• National Cancer Centre - Singapore — Singapore

Malaysia · 1 center

• Sarawak General Hospital — Kuching

Identifiers

NCT: NCT06706076 · BH-30643-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗