BT8009 + Pembrolizumab for Solid Tumors

Not currently recruiting at 27 trial locations

Overseen By Bicycle Tx Limited

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bicycle Tx Limited

Must not be taking: Enfortumab vedotin, ADC vedotin

Disqualifiers: Uncontrolled diabetes, Hypertension, CNS disease, others

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

Compensation: Varies

Number of Visits: 20

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new drug combination, BT8009 (a Bicycle Toxin Conjugate) with pembrolizumab, for people with advanced solid tumors. The focus is on tumors that show Nectin-4 expression or those in patients with kidney issues. Participants might include those who have exhausted standard treatment options and have specific types of cancer, such as urothelial carcinoma, breast cancer, or lung cancer. This trial may suit individuals with solid tumors unresponsive to other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Do I need to stop my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that BT8009, a new cancer treatment, appears promising in early studies. Tests conducted in the lab and on animals before human trials demonstrated that BT8009 effectively targets cancer cells and causes few serious side effects.

When combined with pembrolizumab, an existing cancer drug, BT8009 has shown a manageable safety profile, indicating that side effects are not too severe.

Since this study remains in the early stages, more information is needed to fully understand its safety for humans. However, the initial results are encouraging, suggesting that BT8009, both alone and with pembrolizumab, could potentially treat advanced solid tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BT8009 and its combination with Pembrolizumab because they represent a new approach for treating solid tumors. Unlike traditional chemotherapy, which targets all rapidly dividing cells, BT8009 is a novel compound designed to specifically target cancer cells, potentially reducing side effects and improving effectiveness. When combined with Pembrolizumab, an immunotherapy that helps the immune system recognize and attack cancer cells, it offers a two-pronged approach: precise targeting of tumor cells and enhanced immune response. This combination could provide a more effective and less toxic treatment option compared to standard therapies like traditional chemotherapy and radiation.

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

Research has shown that BT8009, a new cancer treatment known as a Bicycle toxin conjugate, shows promise in targeting Nectin-4, a protein present in many solid tumors. This treatment aims to deliver cancer-fighting agents directly into the tumor, potentially reducing side effects. Early results indicate good safety and potential effectiveness in patients with advanced bladder cancer.

In this trial, some participants will receive BT8009 alone, while others will receive it in combination with pembrolizumab, a well-known cancer drug that helps the immune system attack cancer cells. Previous studies demonstrated that combining BT8009 with pembrolizumab achieved a 60% overall response rate in patients with advanced bladder cancer. These findings suggest that this combination could be effective for solid tumors with Nectin-4. ^{1 3 4 5 6}

Who Is on the Research Team?

Meredith McKean, MD, MPH

Principal Investigator

Tennessee Oncology

Are You a Good Fit for This Trial?

This trial is for adults with advanced cancers like ovarian, breast, lung, and bladder cancer that express Nectin-4. Participants must have tried all standard treatments without success or be unsuitable for them. They should not have had certain other cancers in the last 3 years or conditions like uncontrolled diabetes, active infections, severe nerve damage, or a history of serious skin reactions to similar drugs.

Inclusion Criteria

I have advanced ovarian, fallopian tube, or peritoneal cancer that has worsened after treatment.

My bladder cancer has worsened or returned after my last treatment and I haven't been treated with EV.

My bladder cancer has worsened after treatment.

Exclusion Criteria

I do not have active or untreated brain or spinal cord cancer.

You have a significant increase in troponin levels that could affect your health.

I have not had a fever or needed treatment for an infection in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part A involves dose escalation to evaluate safety and tolerability of BT8009 as monotherapy or in combination with pembrolizumab

28 days per cycle

Weekly visits for dose escalation

Dose Expansion

Part B involves dose expansion to assess clinical activity of BT8009 as monotherapy or in combination with pembrolizumab

Every 8 weeks for 12 months

Visits every 8 weeks

Pharmacokinetics Evaluation

Part D evaluates the pharmacokinetics of BT8009 and MMAE

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BT8009
• Nivolumab
• Pembrolizumab

Trial Overview The study tests BT8009 alone and combined with Pembrolizumab in patients whose tumors show Nectin-4 expression. It's an early-phase trial to find safe doses (Phase I) and then see how well it works (Phase II). The main goals are to check for dose-limiting side effects and measure tumor response rates.

How Is the Trial Designed?

Group I: Part D - BT8009 Monotherapy Supplementary PK Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT8009.

Group II: Part C - Renal Insufficiency BT8009 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT8009.

Group III: Part B-9 - BT8009 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT8009.

Group IV: Part B-8 - BT8009 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT8009.

Group V: Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-Escalation Experimental Treatment 2 Interventions

Participants will receive BT8009 and a standard dose of pembrolizumab.

Group VI: Part A-1 -BT8009 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Participants will receive escalating doses of BT8009.

Group VII: Cohort B-7- BT8009 in Combination with Pembrolizumab Dose Expansion Experimental Treatment 2 Interventions

Participants will receive a selected dose of BT8009 and standard dose of pembrolizumab.

Group VIII: Cohort B-6- BT8009 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT8009.

Group IX: Cohort B-5- BT8009 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT8009.

Group X: Cohort B-4- BT8009 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT8009.

Group XI: Cohort B-3- BT8009 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT8009. .

Group XII: Cohort B-2- BT8009 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT8009.

Group XIII: Cohort B-1 - BT8009 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants will receive a selected dose of BT8009.

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

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9940631/

BT8009; A Nectin-4 Targeting Bicycle Toxin Conjugate for ... Despite excellent data in urothelial cancer, little efficacy data are reported for EV in other Nectin-4 expressing tumors and EV therapy can produce significant ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS4619

A phase 2/3 study of Bicycle toxin conjugate BT8009 ... BT8009 has a low molecular weight and short plasma half-life, with potential to rapidly penetrate solid tumors and reduce toxicity by minimizing ...

3. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jmedchem.2c00065

Discovery of BT8009: A Nectin-4 Targeting Bicycle Toxin ... Bicycle toxin conjugates (BTCs) are a new class of anticancer agents that allow efficient and targeted delivery of toxin payloads into tumors.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04561362

NCT04561362 | Study BT8009-100 in Subjects With Nectin ... This study will assess the safety and tolerability of BT8009 alone and in combination with pembrolizumab in patients with select advanced solid tumors.

5. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-bladder-cancer/160812-asco-2025-duravelo-2-a-phase-2-3-study-of-bicycle-toxin-conjugate-zelenectide-pevedotin-bt8009-targeting-nectin-4-in-patients-with-locally-advanced-or-metastatic-urothelial-cancer.html

ASCO 2025: Duravelo-2: A Phase 2/3 Study of Bicycle ... Results from the ongoing phase 1/2 clinical trial of zelenectide pevedotin (NCT04561362) indicate preliminary antitumor activity and a tolerable safety profile ...

6. bicycletherapeutics.com bicycletherapeutics.com/wp-content/uploads/2024/05/ASCO-2024-Duravelo-2-TiP-Poster-FINAL.pdf

ASCO-2024-Duravelo-2-TiP-Poster-FINAL.pdf This phase 2/3 study evaluates zelenectide pevedotin (BT8009), a Bicycle Toxin Conjugate targeting Nectin-4, for locally advanced or metastatic ...