NCT06706076招募中1 期
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)
BlossomHill Therapeutics58 个研究点 分布在 9 个国家目标入组 675 人开始时间: 2025年1月9日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 675
- 试验地点
- 58
- 主要终点
- Dose-limiting toxicities (DLTs) (Phase 1, Dose Escalation)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 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
- •Has at least 1 measurable target extracranial lesion according to RECIST v1.
- •Eastern Cooperative Oncology Group Performance Status ≤
- •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.
排除标准
- •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.
研究组 & 干预措施
Phase 1 Combination Dose Escalation and Expansion
Experimental
- BH-30643 combo therapy with Carboplatin/Pemetrexed for dose escalation
- BH-30643 combo therapy with Carboplatin/Pemetrexed for dose expansion /optimization at doses determined from dose escalation data
干预措施: BH-30643 combo therapy with Carboplatin/Pemetrexed (Drug)
Phase 1 Monotherapy Dose Escalation and Expansion
Experimental
- BH-30643 monotherapy for dose escalation
- BH-30643 monotherapy for dose expansion/optimization at doses determined from dose escalation data
干预措施: BH-30643 (Drug)
Phase 2
Experimental
BH-30643 administered at the RP2D dose determined in Phase 1
干预措施: BH-30643 (Drug)
结局指标
主要结局
Dose-limiting toxicities (DLTs) (Phase 1, Dose Escalation)
时间窗: 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)
时间窗: Within 21 days of last participant dosed during Dose Expansion/Optimization.
Determine the RP2D for Phase 2.
Objective Response Rate (ORR) (Phase 2)
时间窗: Approximately 3 years after the first participant dosed.
Determine ORR as assessed by Blinded Independent Central Review (BICR).
次要结局
- Safety(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).(Predose and up to 24 hours postdose.)
- Maximum observed plasma concentration (Cmax) of BH-30643 for Single dose (Phase 1).(Predose and up to 24 hours postdose.)
- Time to reach Cmax (Tmax) of BH-30643 for Single dose (Phase 1).(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.(Predose and up to 24 hours postdose.)
- Objective Response Rate (ORR)(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)(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)(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)(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)(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)(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(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).)
- NSCLC-SAQ(From enrollment until the end of treatment, up till patient discontinue from treatment due to any reason (up to approximately 4 years).)
- ERTC-QLC-C30(From enrollment until the end of treatment, up till patient discontinue from treatment due to any reason (up to approximately 4 years).)
- Duration of Response (DOR)(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)(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(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).)
- NSCLC-SAQ(From enrollment until the end of treatment, up till patient discontinues treatment for any reason (up to approximately 4 years).)
研究者
研究点 (58)
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相关资讯
BlossomHill's OMNI-EGFR Inhibitor BH-30643 Yields 45% ORR in C797S-Positive NSCLC- Updated Phase 1/2 SOLARA data show BH-30643 achieved a 45% objective response rate and 88% disease control rate in EGFR C797S-positive NSCLC resistant to prior EGFR inhibitors.
- Among 40 patients with C797S-positive disease, 63% remained on treatment at a median follow-up of 6.9 months, with 98% having received prior osimertinib.
- BH-30643 showed a favorable safety profile at 40-60 mg twice daily, with treatment-related dose reductions in 9% and discontinuations in 3% of 174 patients.
- BlossomHill plans to launch a global Phase 2 trial in C797S-positive NSCLC in Q1 2027, following FDA Fast Track designation for the oral, brain-active inhibitor.8 hours agoEGFR-Mutated NSCLC Pipeline Expands with 30+ Therapies as FDA Approves Dato-DXd and J&J Combination Shows Survival Benefit- The FDA granted accelerated approval to Dato-DXd in June 2025 for adults with locally advanced or metastatic EGFR-mutated NSCLC who progressed after prior EGFR-targeted therapies and platinum-based chemotherapy.
- Johnson & Johnson's Phase 3 MARIPOSA study demonstrated that the combination of RYBREVANT and LAZCLUZE significantly improved overall survival compared to osimertinib in EGFR-mutated NSCLC patients.
- Over 25 companies are developing 30+ therapies for EGFR-mutated NSCLC across various clinical phases, including novel small molecules, monoclonal antibodies, and combination treatments.
- Recent clinical milestones include BlossomHill Therapeutics initiating the SOLARA Phase 1/2 trial for BH-30643 and AstraZeneca receiving Priority Review for Dato-DXd's BLA application.10 months agoBlossomHill Therapeutics Advances EGFR-Mutant NSCLC Treatment with First-in-Class OMNI-EGFR Inhibitor BH-30643- BlossomHill Therapeutics has dosed the first patient in expansion cohorts of the SOLARA Phase 1/2 trial evaluating BH-30643, a first-in-class OMNI-EGFR inhibitor for advanced EGFR-mutant non-small cell lung cancer.
- BH-30643 demonstrates sub-nanomolar potency against classical and atypical EGFR mutations while maintaining activity against T790M and C797S resistance mutations that commonly limit current therapies.
- The expansion cohorts will assess objective response rates across diverse EGFR mutation subtypes, including treatment-naive patients, following successful dose escalation that showed favorable pharmacokinetics and preliminary anti-tumor activity.
- The drug's broad-spectrum approach aims to address multiple EGFR mutations with a single agent while sparing wildtype EGFR and HER2 inhibition for improved tolerability.last yearBlossomHill Therapeutics to Present Novel OMNI-EGFR Inhibitor BH-30643 at AACR 2025 for NSCLC Treatment• BlossomHill Therapeutics will present data on BH-30643, a macrocyclic, mutant-selective OMNI-EGFR inhibitor designed to target multiple EGFR mutations in non-small cell lung cancer, at the 2025 AACR Annual Meeting.
• The novel inhibitor demonstrates potent activity against classical EGFR mutations, atypical mutations, and exon 20 insertions while maintaining effectiveness against common resistance mutations, potentially simplifying treatment selection.
• BH-30643 is currently being evaluated in the Phase 1/2 SOLARA clinical trial for locally advanced or metastatic NSCLC with EGFR or HER2 mutations, with results to be presented on April 29, 2025.last year