BH-30643 for Lung Cancer

(SOLARA Trial)

Recruiting at 32 trial locations

Overseen By Sponsor Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BlossomHill Therapeutics

Disqualifiers: Concurrent malignancy, Oncogenic driver, Uncontrolled condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

266 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BH-30643 for individuals with advanced lung cancer who have specific gene changes (EGFR or HER2 mutations). The goal is to assess the safety and effectiveness of this treatment and determine the optimal dose. The trial consists of two phases: the first phase identifies the correct dose, and the second phase evaluates the treatment's effectiveness at that dose. Eligible participants have lung cancer with these gene changes and have already undergone standard treatments. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from a potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are actively receiving investigational therapies in another clinical study, you may not be eligible to participate.

Is there any evidence suggesting that BH-30643 is likely to be safe for humans?

Research has shown that BH-30643 has a promising safety record in early studies, indicating it is safe for the heart. Participants have tolerated the treatment well during testing. As a Phase 1/2 trial, BH-30643 remains in the early stages of human testing. While there is some evidence of safety, more data is needed to confirm how well people handle the treatment. Overall, initial findings suggest it is fairly safe, but further research is necessary for confirmation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

BH-30643 is unique because it offers a new twice-daily oral dosing method for treating lung cancer, which could improve patient convenience and adherence compared to traditional intravenous infusions. Researchers are excited because this treatment works by optimizing dosage based on data from earlier phases, potentially leading to more effective results with fewer side effects. Additionally, the focus on dose escalation and expansion ensures that the treatment is finely tuned to provide the best possible outcomes for patients.

What evidence suggests that BH-30643 might be an effective treatment for lung cancer?

Research has shown that BH-30643 is a promising new treatment for some lung cancer patients. It targets specific changes in the EGFR and HER2 genes, often found in non-small cell lung cancer (NSCLC). Early studies indicate that BH-30643 can effectively block these changes, potentially stopping cancer cells from growing. This trial will evaluate BH-30643, administered at the recommended dose determined in Phase 1, to specifically attack cancer cells with these changes, causing less harm to healthy cells. Initial tests suggest that BH-30643 has a wide range of anti-tumor effects, making it a hopeful option for those with these genetic changes. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or widespread non-small cell lung cancer that has specific mutations in EGFR or HER2 genes. Participants should be able to take oral medication and have not responded well to previous treatments, if any.

Inclusion Criteria

Has a life expectancy of ≥ 3 months

I can carry out all my self-care but cannot do heavy physical work.

I have received the standard treatments for my condition.

Exclusion Criteria

I do not have any uncontrolled serious health issues.

Actively receiving investigational therapy(ies) in another clinical study

I have had interstitial lung disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

BH-30643 monotherapy for dose escalation to determine the recommended Phase 2 dose (RP2D) and maximum tolerated dose (MTD)

21 days

Multiple visits for dose escalation and monitoring

Phase 1 Dose Expansion/Optimization

BH-30643 monotherapy for dose expansion/optimization at doses determined from dose escalation data

21 days

Multiple visits for dose optimization and monitoring

Phase 2 Treatment

BH-30643 administered at the RP2D dose to evaluate antitumor efficacy and safety

Up to 4 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BH-30643

Trial Overview The study tests BH-30643 capsules taken orally twice daily over 21-day cycles. It aims to find the safest and most effective dose (Phase 1) and then assess its ability to shrink tumors at this dose (Phase 2), focusing on different genetic mutation subtypes.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 1 Intervention

BH-30643 administered at the RP2D dose determined in Phase 1

Group II: Phase 1 Dose Escalation and Expansion Experimental Treatment 1 Intervention

* 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

Who Is Running the Clinical Trial?

BlossomHill Therapeutics

Lead Sponsor

Trials

2

Recruited

340+

Published Research Related to This Trial

BDA-366 is a small-molecule antagonist that specifically targets the BH4 domain of Bcl2, effectively converting Bcl2 from a protector of cells to a promoter of cell death, which is crucial for cancer treatment.

In preclinical studies, BDA-366 demonstrated significant anti-cancer effects against lung cancer xenografts without harming normal tissues, and when combined with mTOR inhibitor RAD001, it showed enhanced efficacy, suggesting a promising new strategy for lung cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small-Molecule Bcl2 BH4 Antagonist for Lung Cancer Therapy. Han, B., Park, D., Li, R., et al.[2022]

In a study of 23 patients with relapsed or refractory small-cell lung cancer, the combination of topotecan and etoposide showed a modest overall response rate of 17.4%, with a median progression-free survival of 4.7 months and median overall survival of 9.5 months.

The treatment was associated with significant toxicities, including severe myelosuppression, with 78.3% of patients experiencing grade 3/4 neutropenia, indicating that while the regimen has some efficacy, it also carries considerable risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of topotecan and etoposide as a salvage treatment for patients with recurrent small cell lung cancer following irinotecan and platinum first-line chemotherapy. Choi, HJ., Cho, BC., Shin, SJ., et al.[2018]

BMS-184476, an analog of paclitaxel, was well tolerated in 56 patients with advanced non-small-cell lung cancer, with only 3.8% of treatment cycles requiring dose reduction and no life-threatening events reported.

The treatment showed antitumor activity, with 14.3% of patients achieving partial responses and a median overall survival of 10 months, indicating its potential effectiveness in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of the novel taxane BMS-184476 as second-line in non-small-cell lung cancer. Camps, C., Felip, E., Sanchez, JM., et al.[2020]

The combination of ABT-737, a Bcl-2 family protein inhibitor, and sorafenib, an oncogenic kinase inhibitor, significantly enhances the effectiveness of cancer treatment by inducing apoptosis in human oral cancer cells (MC-3 and HSC-3) more than either drug alone.

This combination therapy appears to overcome drug tolerance to ABT-737 by altering specific proteins (Bax and Bak) and activating pathways (ERK and STAT3), suggesting a promising new strategy for treating resistant oral cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib potentiates ABT-737-induced apoptosis in human oral cancer cells. Kim, LH., Shin, JA., Jang, B., et al.[2022]

In a study involving 623 patients with advanced non-small-cell lung cancer, the addition of bexarotene to standard chemotherapy (cisplatin/vinorelbine) did not significantly improve overall survival compared to chemotherapy alone.

However, a subgroup of patients treated with bexarotene who developed high-grade hypertriglyceridemia showed a potential survival benefit, suggesting that triglyceride response could serve as a biomarker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase III trial comparing bexarotene (L1069-49)/cisplatin/vinorelbine with cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT I. Ramlau, R., Zatloukal, P., Jassem, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06706076

NCT06706076 | A Study of BH-30643 in Subjects With ... This Phase1/2, open label, multicenter study will assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary anti-tumor ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS8663

A phase 1/2 open-label, multicenter, first-in-human study of ... BH-30643 is a first-in-class EGFR TKI with a novel macrocyclic structure offering potent, reversible, mutant selective inhibition of classical and atypical ...

3. bhtherapeutics.com bhtherapeutics.com/pipeline/bh-30643/

BH-30643 HER2 activating mutations have been identified in approximately 4% of patients with NSCLC and are linked to unfavorable patient outcomes. Unfortunately, there ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT490842

Anti-tumor activity of BH-30643, a novel macrocyclic kinase ... Conclusions: These preclinical studies demonstrate broad activity of BH-30643 against classical and atypical EGFR activating mutations, EGFR ex20ins, as well as ...

5. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/blossomhill-doses-first-patient-in-expanded-phase-1-2-solara-trial-cohorts/

Blossomhill Doses First Patient in Expanded Phase 1/2 ... The trial's success hinges on BH-30643 replicating the early signs of efficacy in a larger and more diverse patient population. Key factors to ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/557963

A Study of BH-30643 in Subjects With Locally Advanced or ... 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 ...