BPT567 for Cancer

(SUMMIT-1 Trial)

Recruiting at 2 trial locations

Overseen By Sujatha Venugopal Prasad, M. Sc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bright Peak Therapeutics Inc

Must not be taking: Immunosuppressants, IL-18 therapy

Disqualifiers: HIV, Hepatitis, Brain metastasis, others

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

Compensation: Varies

Number of Visits: 1

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a first-in-human Phase Ia/Ib, open-label, multicenter, dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and maximum tolerated dose (MTD) or maximum adminstered dose (MAD) of BPT567 in patients with advanced solid tumors, and establish the recommended dose for expansion cohorts.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. You must not have had systemic small molecule therapy or radiation therapy within 28 days before the first dose, and certain biologic agents must be stopped for a specific period as well.

What data supports the effectiveness of the drug BPT567 for cancer?

Research shows that bevacizumab, a component of BPT567, has been effective in improving progression-free survival and overall response rates in various cancers, including breast and lung cancer, when combined with other chemotherapy drugs. ^{1 2 3 4 5}

What safety data exists for BPT567 in humans?

The research articles discuss the safety of pembrolizumab, a treatment similar to BPT567, which has been used in various cancers. In trials, 44% of patients experienced immune-related side effects, and other studies reported multiple high-grade immune-related adverse events, such as inflammation of the lungs and thyroid. This suggests that while effective, treatments like BPT567 may have significant side effects. ^{6 7 8 9 10}

How does the drug BPT567 differ from other cancer treatments?

The research does not provide specific information about BPT567, but it mentions lapatinib, a drug that targets HER2 and EGFR, which are proteins involved in cancer growth. If BPT567 is similar to lapatinib, it might work by blocking these proteins to slow down or stop cancer growth, which could be a unique approach compared to other treatments. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for patients with advanced solid tumors who are eligible to receive a new treatment. Specific eligibility details aren't provided, but typically participants must be adults with measurable cancer, good organ function, and no serious concurrent health issues.

Inclusion Criteria

Measurable disease per RECIST 1.1

I am fully active or can carry out light work.

Life expectancy of at least 3 months

Exclusion Criteria

Certain clinically significant intercurrent disease

Known HIV seroposivitiy, although patients treated for HIV with no detectable viral load for at least 1 month while on a stable regimen of agents are permitted

I haven't had a live virus vaccine in the last 30 days or a COVID vaccine in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BPT567 at multiple dose levels to define MTD or MAD

28 days per cycle

Cycle 1 (Days 1, 2, 4, 8, 15 & 22), Cycles 2 & 3 (Days 1 & 15), Cycles 4 & beyond (Day 1)

Dose Expansion

Participants receive BPT567 at the recommended dose for expansion cohorts

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BPT567

Trial Overview The study is testing BPT567's safety and how well it's tolerated in humans. It will gradually increase doses to find the highest dose patients can take without severe side effects (MTD/MAD) and determine the right dose for further studies.

Participant Groups

Group I: Phase 1b Dose Expansion Experimental Treatment 1 Intervention

Study drug BPT567 at recommended dose for expansion (RDE) cohorts

Group II: Phase 1a Dose Escalation Experimental Treatment 1 Intervention

Study drug BPT567 at multiple dose levels to define MTD or MAD

Who Is Running the Clinical Trial?

Bright Peak Therapeutics Inc

Lead Sponsor

Trials

1

Recruited

100+

Findings from Research

A nine-protein signature score, called the vascular endothelial growth factor inhibition response predictor (ViRP), was developed to accurately predict which HER2-negative breast cancer patients would benefit from treatment with bevacizumab combined with chemotherapy, showing a high predictive accuracy (AUC = 0.85).

The ViRP score was significantly lower in patients who achieved a pathologic complete response (pCR) and low residual cancer burden, indicating its potential as a biomarker to identify patients likely to respond well to this antiangiogenic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein Signature Predicts Response to Neoadjuvant Treatment With Chemotherapy and Bevacizumab in HER2-Negative Breast Cancers. Haugen, MH., Lingjærde, OC., Hedenfalk, I., et al.[2022]

The combination of bevacizumab with paclitaxel shows confirmed safety and efficacy in treating metastatic breast cancer, with a median progression-free survival of 13 months observed in a study of 124 patients.

High expression of VEGF receptor 3 (VEGFR3) is linked to better clinical responses, while high levels of VEGFR1 are associated with poorer survival outcomes, suggesting potential biomarkers for treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and bevacizumab as first line combined treatment in patients with metastatic breast cancer: the Hellenic Cooperative Oncology Group experience with biological marker evaluation. Fountzilas, G., Kourea, HP., Bobos, M., et al.[2022]

In the E2100 phase III trial involving patients with HER2-negative metastatic breast cancer, the combination of paclitaxel and bevacizumab significantly improved progression-free survival (PFS) compared to paclitaxel alone, with median PFS increasing from 5.8 months to 11.3 months.

The overall response rate (ORR) also more than doubled with the addition of bevacizumab, rising from 22.2% to 48.9%, demonstrating a strong therapeutic effect of this combination treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. Gray, R., Bhattacharya, S., Bowden, C., et al.[2022]

In a retrospective analysis of 217 patients from the ECOG 4599 study, those who received bevacizumab (BV) maintenance therapy after induction treatment showed significantly longer progression-free survival (4.4 months) compared to those who received carboplatin and paclitaxel (CP) alone (2.8 months).

The safety profile of BV maintenance was favorable, with less than 1% of patients experiencing severe hematological toxicities and no severe nausea, vomiting, or diarrhea, indicating that BV can be a safe option for maintaining treatment benefits in non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab maintenance in patients with advanced non-small-cell lung cancer, clinical patterns, and outcomes in the Eastern Cooperative Oncology Group 4599 Study: results of an exploratory analysis. Lopez-Chavez, A., Young, T., Fages, S., et al.[2015]

In a study of 195 patients with metastatic colorectal cancer, the combination of bevacizumab and FOLFIRI as a second-line treatment after oxaliplatin failure showed a median progression-free survival (PFS) of 8.3 months, comparable to 7.8 months for those receiving bevacizumab with FOLFOX after irinotecan failure.

Both treatment regimens demonstrated similar overall survival rates, with 21.6 months for FOLFIRI+BV and 16.5 months for FOLFOX+BV, indicating that FOLFIRI can be an effective alternative in this patient population, with manageable adverse events like hypertension and bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in patients with metastatic colorectal cancer who were previously treated with oxaliplatin-containing regimens: a multicenter observational cohort study (TCTG 2nd-BV study). Moriwaki, T., Bando, H., Takashima, A., et al.[2021]

The PePS2 trial demonstrated that pembrolizumab can be safely administered to patients with non-small-cell lung cancer (NSCLC) and a performance status of 2, with a toxicity rate of 28% and no severe treatment-related adverse events, indicating a manageable safety profile.

Efficacy outcomes showed that 38% of first-line and 36% of subsequent-line patients experienced durable clinical benefit, with higher response rates correlating with tumor proportion scores, suggesting that pembrolizumab is effective for this underserved patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. Middleton, G., Brock, K., Savage, J., et al.[2020]

In a study of 56 patients with incidental prostate cancer, the RTUR-PCa procedure showed a low prostate-specific antigen (PSA) failure rate of only 5.9% over a mean follow-up of 64.1 months, indicating effective oncological outcomes.

While bladder neck contracture occurred in 43.1% of patients, there were no serious complications like water intoxication or the need for transfusions, and temporary postoperative incontinence resolved within 3 months, suggesting RTUR-PCa is a safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of incidental prostate cancer by radical transurethral resection of prostate cancer. Morita, M., Matsuura, T.[2013]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

A middle-aged patient with microsatellite instability-high (MSI-H) metastatic colorectal cancer experienced multiple high-grade immune-related adverse events (irAEs) during immunotherapy, including serious conditions like pneumonitis and transverse myelitis.

Genomic profiling indicated a high tumor mutational burden, and cytokine analysis suggested potential biomarkers for predicting irAEs, highlighting the need for further research into the relationship between MSI-H mCRC and irAEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple high-grade and rare immune-related adverse events in a colon cancer patient with genomic and cytokine profiling. Tyan, K., Abu-Shawer, O., Baginska, J., et al.[2022]

Pembrolizumab, when combined with chemotherapy, significantly improves pathological complete response (pCR) and event-free survival (EFS) in patients with high-risk, early-stage triple-negative breast cancer, as shown in the KEYNOTE-522 trial with 123 EFS events in the pembrolizumab group compared to 93 in the control group.

Despite 44% of patients experiencing immune-related adverse reactions, the benefits of pembrolizumab, including a 7.5% absolute improvement in pCR rates, support its use as an effective neoadjuvant and adjuvant treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer. Shah, M., Osgood, CL., Amatya, AK., et al.[2023]

Stereotactic radiosurgery (SRS) is a safe and effective treatment for brain metastases from breast cancer, showing a median survival time of 11.4 months and 1-year overall survival rates of 50%.

Patients with HER2-overexpressing tumors, particularly those receiving lapatinib-based therapy, experienced significantly better local tumor control and longer survival compared to those not receiving lapatinib, highlighting the potential synergistic effects of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impacts of HER2-overexpression and molecular targeting therapy on the efficacy of stereotactic radiosurgery for brain metastases from breast cancer. Yomo, S., Hayashi, M., Cho, N.[2021]

In a phase II trial involving 55 patients with progressive breast cancer brain metastasis (BCBM) after whole brain radiotherapy, patupilone achieved only a 27% CNS progression-free survival at 3 months, falling short of the hypothesized 35%.

The treatment was associated with significant gastrointestinal toxicity, with 87% of patients experiencing diarrhea, and 25% suffering from severe (grade 3 and 4) adverse events, indicating a need for caution in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of patupilone in patients with brain metastases from breast cancer. Peereboom, DM., Murphy, C., Ahluwalia, MS., et al.[2021]

In a retrospective study of seven breast cancer patients with inoperable brain metastases, bevacizumab-based chemotherapy (BBCT) followed by whole-brain radiation therapy (WBRT) showed no severe brain toxicity, indicating a potentially safe treatment sequence.

The most common side effects reported were mild to moderate, including nausea and headache, and there were no signs of serious complications like necrosis or cerebral ischemia, suggesting that BBCT can be administered safely before WBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary experience of whole-brain radiation therapy (WBRT) in breast cancer patients with brain metastases previously treated with bevacizumab-based chemotherapy. Chira, C., Jacob, J., Derhem, N., et al.[2021]

The H460/MX20 cell xenograft model in athymic nude mice successfully maintains the original characteristics and multidrug resistance (MDR) phenotype of the ABCG2-overexpressing H460 cells, making it a reliable model for studying drug resistance in vivo.

Lapatinib, an ABCG2 inhibitor, effectively reverses the resistance of these xenograft cells to drugs like mitoxantrone and topotecan, suggesting potential therapeutic strategies to overcome MDR in lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABCG2-overexpressing H460/MX20 cell xenografts in athymic nude mice maintained original biochemical and cytological characteristics. Zhang, W., Chen, Z., Chen, L., et al.[2018]

Lapatinib ditosylate is a dual tyrosine kinase inhibitor targeting ErbB-2 and EGFR, which are important proteins involved in the growth of certain solid tumors.

This drug is being developed by GlaxoSmithKline plc, indicating ongoing research into its efficacy and safety for treating cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lapatinib ditosylate GlaxoSmithKline. Kim, TE., Murren, JR.[2007]

References

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

Protein Signature Predicts Response to Neoadjuvant Treatment With Chemotherapy and Bevacizumab in HER2-Negative Breast Cancers. [2022]

2. Greece pubmed.ncbi.nlm.nih.gov

Paclitaxel and bevacizumab as first line combined treatment in patients with metastatic breast cancer: the Hellenic Cooperative Oncology Group experience with biological marker evaluation. [2022]

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

Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. [2022]

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

Bevacizumab maintenance in patients with advanced non-small-cell lung cancer, clinical patterns, and outcomes in the Eastern Cooperative Oncology Group 4599 Study: results of an exploratory analysis. [2015]

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

Bevacizumab in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in patients with metastatic colorectal cancer who were previously treated with oxaliplatin-containing regimens: a multicenter observational cohort study (TCTG 2nd-BV study). [2021]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. [2020]

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

Successful treatment of incidental prostate cancer by radical transurethral resection of prostate cancer. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Multiple high-grade and rare immune-related adverse events in a colon cancer patient with genomic and cytokine profiling. [2022]

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

FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer. [2023]

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

Impacts of HER2-overexpression and molecular targeting therapy on the efficacy of stereotactic radiosurgery for brain metastases from breast cancer. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Phase II trial of patupilone in patients with brain metastases from breast cancer. [2021]

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

Preliminary experience of whole-brain radiation therapy (WBRT) in breast cancer patients with brain metastases previously treated with bevacizumab-based chemotherapy. [2021]

14. England pubmed.ncbi.nlm.nih.gov

ABCG2-overexpressing H460/MX20 cell xenografts in athymic nude mice maintained original biochemical and cytological characteristics. [2018]

15. England pubmed.ncbi.nlm.nih.gov

Lapatinib ditosylate GlaxoSmithKline. [2007]