BT8009 + Pembrolizumab for Solid Tumors
Recruiting in Palo Alto (17 mi)
+26 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Bicycle Tx Limited
Must not be taking: Enfortumab vedotin, ADC vedotin
Disqualifiers: Uncontrolled diabetes, Hypertension, CNS disease, others
No Placebo Group
Breakthrough Therapy
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.
12345What 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.
12367What 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.
12358Eligibility 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.
+16 more
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.
+10 more
Participant Groups
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.
13Treatment groups
Experimental Treatment
Group I: Part D - BT8009 Monotherapy Supplementary PKExperimental Treatment1 Intervention
Participants will receive a selected dose of BT8009.
Group II: Part C - Renal Insufficiency BT8009 Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Participants will receive a selected dose of BT8009.
Group III: Part B-9 - BT8009 Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Participants will receive a selected dose of BT8009.
Group IV: Part B-8 - BT8009 Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Participants will receive a selected dose of BT8009.
Group V: Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-EscalationExperimental Treatment2 Interventions
Participants will receive BT8009 and a standard dose of pembrolizumab.
Group VI: Part A-1 -BT8009 Monotherapy Dose EscalationExperimental Treatment1 Intervention
Participants will receive escalating doses of BT8009 via IV.
Group VII: Cohort B-7- BT8009 in Combination with Pembrolizumab Dose ExpansionExperimental Treatment2 Interventions
Participants will receive a selected dose of BT8009 and standard dose of pembrolizumab.
Group VIII: Cohort B-6- BT8009 Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Participants will receive a selected dose of BT8009.
Group IX: Cohort B-5- BT8009 Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Participants will receive a selected dose of BT8009.
Group X: Cohort B-4- BT8009 Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Participants will receive a selected dose of BT8009.
Group XI: Cohort B-3- BT8009 Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Participants will receive a selected dose of BT8009. .
Group XII: Cohort B-2- BT8009 Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Participants will receive a selected dose of BT8009.
Group XIII: Cohort B-1 - BT8009 Monotherapy Dose ExpansionExperimental Treatment1 Intervention
Participants will receive a selected dose of BT8009.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Princess Margaret Cancer CentreToronto, Canada
Mary Crowley Cancer Research CenterDallas, TX
Thomas Jefferson University, Sidney Kimmel Cancer CenterPhiladelphia, PA
Tennessee Oncology, PLLCNashville, TN
More Trial Locations
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Who Is Running the Clinical Trial?
Bicycle Tx LimitedLead Sponsor
BicycleTx LimitedLead Sponsor
References
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]The FDA approved pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.
Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint, which may be engaged by cells in the tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda®, MK-3475) is a potent and highly selective humanized mAb of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances the functional activity of T cells to facilitate tumor regression and ultimately immune rejection. Pembrolizumab binds to human and cynomolgus monkey PD-1 with picomolar affinity and blocks the binding of human and cynomolgus monkey PD-1 to PD-L1 and PD-L2 with comparable potency. Pembrolizumab binds both the C'D and FG loops of PD-1. Pembrolizumab overcomes human and cynomolgus monkey PD-L1-mediated immune suppression in T-cell cultures by enhancing IL2 production following staphylococcal enterotoxin B stimulation of healthy donor and cancer patient cells, and IFNγ production in human primary tumor histoculture. Ex vivo and in vitro studies with human and primate T cells show that pembrolizumab enhances antigen-specific T-cell IFNγ and IL2 production. Pembrolizumab does not mediate FcR or complement-driven effector function against PD-1-expressing cells. Pembrolizumab displays dose-dependent clearance and half-life in cynomolgus monkey pharmacokinetic and toxicokinetic studies typical for human IgG4 antibodies. In nonhuman primate toxicology studies, no findings of toxicologic significance were observed. The preclinical data for pembrolizumab are consistent with the clinical anticancer activity and safety that has been demonstrated in human clinical trials.
FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]On December 18, 2015, the FDA granted regular approval to pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) for treatment of patients with unresectable or metastatic melanoma based on results of two randomized, open-label, active-controlled clinical trials. In trial PN006, 834 patients with ipilimumab-naïve metastatic melanoma were randomized (1:1:1) to pembrolizumab 10 mg/kg i.v. every 2 or 3 weeks until disease progression or ipilimumab 3 mg/kg every 3 weeks for up to four doses. In trial PN002, 540 patients with ipilimumab-refractory metastatic melanoma were randomized (1:1:1) to pembrolizumab 2 or 10 mg/kg i.v. every 3 weeks or to investigator's choice of chemotherapy. In trial PN006, patients randomized to pembrolizumab demonstrated a statistically significant improvement in overall survival compared with ipilimumab [every-2-week arm: hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.47-0.83; P < 0.001; every-3-week arm: HR = 0.69; 95% CI, 0.52-0.90; P = 0.004]. In both trials, patients receiving pembrolizumab demonstrated statistically significant improvements in progression-free survival. The most common (≥2%) immune-mediated adverse reactions in a pooled safety analysis were hypothyroidism, pneumonitis, and hyperthyroidism. Key considerations for approval were determination of pembrolizumab dose and interpretation of tumor response-based endpoints using RECIST or immune-related RECIST. Clin Cancer Res; 23(19); 5661-5. ©2017 AACR.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]Pembrolizumab (Keytruda) has been approved to treat metastatic or locally advanced esophageal or gastroesophageal junction cancer. It is used in combination with platinum- and fluoropyrimidine-based chemotherapy.