BT5528 for Solid Cancers

Recruiting at 25 trial locations

Overseen By BicycleTx Limited

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bicycle Tx Limited

Must not be taking: CYP3A4 inhibitors, P-gp inhibitors

Disqualifiers: Untreated CNS metastases, Uncontrolled hypertension, HIV/AIDS, Hepatitis B/C, others

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

Compensation: Varies

Number of Visits: 16

288 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial is evaluating a drug called BT5528 alone and in combination with nivolumab in participants with advanced solid tumors historically known for expression of EphA2. The main goals of this study are to: * Find the recommended dose(s) of BT5528 that can be given safely to participants alone and in combination with nivolumab * Learn more about the side effects of BT5528 * Learn about how effective BT5528 is for the treatment of ovarian cancer, urothelial/bladder cancer, lung cancer (NSCLC), triple-negative breast cancer, head and neck cancer (HNSCC), and gastric/upper gastrointestinal cancer. * Learn more about BT5528 therapy alone and in combination with nivolumab.

Will I have to stop taking my current medications?

The trial requires that you stop chemotherapy treatments at least 14 days before starting the study treatment and other anticancer treatments within 28 days or 5 half-lives, whichever is shorter. You also cannot be on strong inhibitors or inducers of CYP3A4 or strong inhibitors of P-gp. If you are on any of these medications, you may need to stop them before participating.

What data supports the effectiveness of the drug BT5528 for solid cancers?

Nivolumab, a component of the treatment, has shown effectiveness in treating various solid cancers like non-small cell lung cancer and melanoma by helping the immune system better recognize and attack cancer cells. ^{1 2 3 4 5}

What safety information is available for BT5528 and related treatments like Nivolumab (Opdivo) in humans?

Nivolumab (Opdivo) has been studied for safety in humans, showing common side effects like fatigue, diarrhea, and rash, and some rare but serious blood-related issues. While generally tolerable, it can cause severe immune-related side effects in some patients. ^{1 6 7 8 9}

What makes the drug BT5528 combined with Nivolumab unique for treating solid cancers?

BT5528 combined with Nivolumab is unique because it involves a novel approach using a combination of a new treatment (BT5528) with Nivolumab, a PD-1 inhibitor that helps the immune system recognize and attack cancer cells. This combination may offer a new option for patients with solid cancers, especially those who have not responded to other treatments. ^{1 2 3 10 11}

Research Team

Meredith McKean, MD, MPH

Principal Investigator

Sarah Cannon and HCA Research Institute

Eligibility Criteria

Adults with advanced solid tumors known for high EphA2 expression, including ovarian, lung (NSCLC), triple-negative breast, gastric/GI, head and neck, and urothelial cancers. Participants must have tried all other treatments without success or be ineligible for them. They need proper organ function and agree to use effective contraception.

Inclusion Criteria

I am fully active or can carry out light work.

Must be willing and able to comply with the protocol and study procedures

My kidney, liver, blood, and clotting functions are normal.

Exclusion Criteria

I am not on medication that strongly affects certain liver enzymes or a specific drug transporter.

I have brain metastases or leptomeningeal disease that hasn't been treated.

I have not received a live vaccine in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I - Dose Escalation

Cohorts of participants receive increasing doses of BT5528 alone and in combination with nivolumab to assess safety and determine the recommended Phase II dose(s).

28 days per cycle, multiple cycles

Weekly visits for dose administration and monitoring

Phase II - Dose Expansion

Participants receive the selected dose of BT5528 as a monotherapy to evaluate clinical activity.

28 days per cycle, multiple cycles

Visits every 8 weeks for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment.

6-12 months

Assessments every 8 weeks up to 6 months, then every 16 weeks up to 12 months

Treatment Details

Interventions

• BT5528
• Nivolumab

Trial Overview The trial is testing the safety and effectiveness of a new drug called BT5528 alone and in combination with nivolumab against various advanced solid tumors. It aims to determine safe dosages, understand side effects better, and evaluate how well BT5528 works on these cancers.

Participant Groups

Group I: Phase II - Dose expansion 1 (BT5528) Experimental Treatment 1 Intervention

A cohort of participants will receive the selected dose of BT5528 as a monotherapy. It is expected that up to 164 patients have solid tumors (Cohort 1: urothelial cancers, Cohort 2: ovarian cancer, Cohort 3: non-small cell lung cancer, Cohort 4: head and neck cancer, Cohort 5: triple-negative breast cancer, and Cohort 6: gastric/upper gastrointestinal cancer) historically known for high expression of EphA2 will participate in this dose-expansion arm, Cohort 7: urothelial MMAE exposed, Cohort 8: head and neck squamous cell carcinoma

Group II: Phase I - Dose escalation combination (BT5528 & nivolumab) Experimental Treatment 2 Interventions

Cohorts of participants will receive increasing doses of BT5528 and a standard dose of nivolumab. It is expected that up to 24 participants will participate in this dose-escalation combination arm.

Group III: Phase I - Dose escalation (BT5528) Experimental Treatment 1 Intervention

Cohorts of participants will receive increasing doses of BT5528. It is expected that up to 72 participants will participate in this dose escalation arm.

Who Is Running the Clinical Trial?

Bicycle Tx Limited

Lead Sponsor

Trials

2

Recruited

620+

BicycleTx Limited

Lead Sponsor

Trials

5

Recruited

1,800+

Findings from Research

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab significantly improved overall survival and progression-free survival in patients with unresectable or metastatic melanoma compared to dacarbazine, with hazard ratios of 0.42 and 0.43 respectively, based on a trial involving 418 patients.

The most common side effects of nivolumab included fatigue, diarrhea, and rash, but it was still considered to have a favorable benefit-risk profile compared to dacarbazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. Beaver, JA., Theoret, MR., Mushti, S., et al.[2018]

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., et al.[2023]

Nivolumab, an immune checkpoint inhibitor for metastatic melanoma, can cause immune-related adverse events (irAEs) such as colitis, which were observed in two patients after treatment.

The development of these irAEs is linked to a Th1 dominant immune response, and serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) may serve as potential biomarkers to monitor and manage these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports. Yoshino, K., Nakayama, T., Ito, A., et al.[2020]

Nivolumab, a monoclonal antibody used to treat recurrent renal cell carcinoma, can cause significant immune-related adverse events, such as hepatitis and adrenalitis, as seen in a case study of a 66-year-old male patient.

Prompt recognition and management of these side effects are crucial; in this case, the patient's hepatitis improved with methylprednisolone, and adrenalitis was treated with fludrocortisone, leading to normalization of symptoms and electrolyte levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? Özyurt, E., Özçelik, S., Sürmeli, H., et al.[2022]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab (OPDIVO) received accelerated FDA approval for treating unresectable or metastatic melanoma based on a 31.7% objective response rate in a study of 120 patients, showing promising efficacy after prior treatments.

The treatment demonstrated durable responses, with 87% of responding patients maintaining their response for at least 6 months, although it carries risks of immune-mediated adverse reactions that were monitored in a safety assessment of 268 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. Hazarika, M., Chuk, MK., Theoret, MR., et al.[2023]

References

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

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

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

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]

5. England pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. [2018]

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

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. [2018]

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

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]

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

Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports. [2020]

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

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]

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

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. [2023]