BH-30643 for Lung Cancer

(SOLARA Trial)

Recruiting at 7 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

Trial Summary

What is the purpose of this trial?

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.

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.

How is the drug BH-30643 different from other lung cancer treatments?

BH-30643 is unique because it targets the BH4 domain of the Bcl2 protein, which is crucial for preventing cell death. By binding to this domain, it turns Bcl2 from a survival molecule into one that induces cell death, offering a novel approach to treating lung cancer compared to traditional therapies. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase II trial of the novel taxane BMS-184476 as second-line in non-small-cell lung cancer. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Sorafenib potentiates ABT-737-induced apoptosis in human oral cancer cells. [2022]

3. United States 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Small-Molecule Bcl2 BH4 Antagonist for Lung Cancer Therapy. [2022]

5. Germany 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. [2018]