BT8009 + Pembrolizumab for Solid Tumors

Recruiting at 26 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

329 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a Phase I/II, multicenter, first-in-human, open-label dose-escalation study of BT8009 given as a single agent and in combination with pembrolizumab in participants with advanced solid tumors associated with Nectin-4 expression or in participants with advanced solid tumor malignancies having renal insufficiency. The primary endpoints are: Dose limiting toxicities (Parts A-1 and A-2), Overall response rate per RECIST v1.1 (Parts B1-B7), Safety and tolerability (Parts B-8, B-9 and C), and characterization of the pharmacokinetics (Part D).

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.

What data supports the effectiveness of the drug BT8009 + Pembrolizumab for solid tumors?

Pembrolizumab, a component of the treatment, has shown effectiveness in treating various cancers, including melanoma and non-small cell lung cancer, by enhancing the immune system's ability to fight tumors. It has been approved for use in several cancer types, indicating its potential benefit in treating solid tumors. ^{1 2 3 4 5}

What safety information is available for Pembrolizumab (Keytruda) in humans?

Pembrolizumab (Keytruda) has been associated with some side effects, including fatigue, cough, nausea, skin rash, and diarrhea. More serious immune-related side effects can include lung inflammation (pneumonitis), liver inflammation (hepatitis), and thyroid problems, occurring in a small percentage of patients. ^{1 2 3 6 7}

What makes the drug BT8009 + Pembrolizumab unique for treating solid tumors?

BT8009 + Pembrolizumab is unique because it combines a Bicycle Toxin Conjugate (BT8009) with Pembrolizumab, a PD-1 inhibitor that enhances the immune system's ability to fight cancer by blocking a pathway that tumors use to hide from immune cells. This combination aims to target and kill cancer cells more effectively by using both a targeted toxin and an immune checkpoint inhibitor. ^{1 2 3 5 8}

Research Team

Meredith McKean, MD, MPH

Principal Investigator

Tennessee Oncology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 via IV.

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+

Findings from Research

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]

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, 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]

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) 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) 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 (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]

References

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

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

5. United States 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. [2021]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]