BT5528 for Solid Cancers

Not currently recruiting at 31 trial locations

Overseen By Judy Wang, MD

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug, BT5528, for treating various advanced solid cancers, including ovarian, lung, and bladder cancer. Researchers aim to determine the safest and most effective dose of BT5528, both alone and in combination with nivolumab, an immunotherapy. Participants with specific cancer types that have not responded to standard treatments may be suitable, especially if their cancer has progressed despite previous therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found BT5528 to be safe for patients, with most side effects being mild. No major safety concerns emerged. Research also shows that BT5528, when used with nivolumab, remains safe, with most side effects being mild and manageable.

Since BT5528 is still in the early stages of testing, researchers continue to study its safety. However, early results appear promising. Further research will provide a better understanding of its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BT5528 because it targets EphA2, a protein often overexpressed in certain solid tumors, like urothelial, ovarian, and lung cancers. This targeted approach is different from standard chemotherapy, which attacks all rapidly dividing cells and can cause significant side effects. BT5528 is an antibody-drug conjugate, which means it delivers a potent cancer-killing agent directly to the tumor cells, potentially sparing healthy cells and reducing side effects. Additionally, combining BT5528 with nivolumab, an immune checkpoint inhibitor, might enhance the immune system's ability to fight cancer, offering a novel combination approach not seen in conventional treatments.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research shows that BT5528 has demonstrated early signs of fighting tumors in patients with solid tumors, such as ovarian, bladder, and lung cancers. Studies indicate that patients tolerated BT5528 well, which is encouraging for those seeking new treatment options. In this trial, some participants will receive BT5528 alone, while others will receive a combination of BT5528 and nivolumab, a drug already approved for some cancers. Nivolumab has successfully treated cancers like head and neck cancer and a type of bladder cancer called urothelial carcinoma. Together, BT5528 and nivolumab could offer a new approach to treating cancers with the EphA2 protein, which has been difficult to target in the past. ^{1 4 6 7 8}

Who Is on the Research Team?

Meredith McKean, MD, MPH

Principal Investigator

Sarah Cannon and HCA Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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, 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 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 (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]

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 (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, 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 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, 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04180371

Study BT5528-100 in Patients With Advanced Solid ... Learn about how effective BT5528 is for the treatment of ovarian cancer, urothelial/bladder cancer, lung cancer (NSCLC), triple-negative breast cancer, head and ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39231383/

Results From First-in-Human Phase I Dose-Escalation ... BT5528 was well tolerated and demonstrated favorable and preliminary antitumor activity. We believe these data provide preliminary ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-02918

Study BT5528-100 in Patients With Advanced Solid ... This clinical trial is evaluating a drug called BT5528 alone and in combination with nivolumab in participants with advanced solid tumors historically known ...

4. investors.bicycletherapeutics.com investors.bicycletherapeutics.com/news-releases/news-release-details/bicycle-therapeutics-announces-bt5528-phase-i-dose-escalation

Bicycle Therapeutics Announces BT5528 Phase I Dose ... BT5528, a BTC targeting EphA2, a target for which prior antibody-based approaches have been unsuccessful, has demonstrated anti-tumor activity and ...

5. onclive.com onclive.com/view/bicycle-toxin-conjugates-showcase-early-activity-and-tolerability-in-urothelial-ovarian-cancers

Bicycle Toxin Conjugates Showcase Early Activity and ... The bicycle toxin conjugates (BTCs) BT5528 and BT8009 have showcased preliminary signs of antitumor activity and encouraging tolerability ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.TPS3655

BT5528-100 phase I/II study of the safety ... A first-in-human study to investigate safety and efficacy of BT5528 in indications with evidence of EphA2 expression including non-small-cell lung cancer ( ...

7. investors.bicycletherapeutics.com investors.bicycletherapeutics.com/news-releases/news-release-details/bicycle-therapeutics-announces-first-patient-dosed-expansion

Press Release “We believe EphA2 is an attractive target for cytotoxin delivery and BT5528 has the potential to overcome the significant safety concerns seen ...

8. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2021-0288.html

Phase I/II Study of the Safety, Pharmacokinetics, and ... This clinical trial is evaluating a drug called BT5528 alone and in combination with nivolumab in participants with advanced solid tumors historically known for ...