BT5528 for Solid Cancers
Recruiting in Palo Alto (17 mi)
+25 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: CYP3A4 inhibitors, P-gp inhibitors
Disqualifiers: Untreated CNS metastases, Uncontrolled hypertension, HIV/AIDS, Hepatitis B/C, others
No Placebo Group
Breakthrough Therapy
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.
12345What 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.
16789What 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.
1351011Eligibility 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.
+11 more
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.
+23 more
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: Phase II - Dose expansion 1 (BT5528)Experimental Treatment1 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 Treatment2 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 Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sarah Cannon and HCA Research InstituteNashville, TN
University of California - Irvine Medical CenterOrange, CA
Stephenson Cancer Center (Oklahoma University)Oklahoma City, OK
Sarah Cannon Research Institute at HealthONEDenver, CO
More Trial Locations
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Who Is Running the Clinical Trial?
Bicycle Tx LimitedLead Sponsor
BicycleTx LimitedLead Sponsor
References
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Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]Progress in the treatment of patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) has been limited. An improvement in the understanding of tumor immunosurveillance has resulted in the development of the immune checkpoint inhibitors such as nivolumab. Nivolumab (Opdivo(®)), a human immunoglobulin (Ig)G4 anti-programmed death (PD)-1 monoclonal antibody, was the first PD-1 inhibitor approved in the treatment of patients with advanced stage squamous cell NSCLC following platinum-based chemotherapy. CHECKMATE 017, a randomized phase III study of second-line nivolumab versus docetaxel, significantly improved overall survival (OS), progression-free survival (PFS), patient reported outcomes and the safety and tolerability favored patients treated with nivolumab. The ligand (PD-L1) expression did not predict for outcome. In this paper, we review the role of nivolumab in the treatment of NSCLC with particular attention on recent studies, ongoing combination studies, toxicity profile, current and potential predictive biomarkers.
Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy. In the pivotal CheckMate 017 trial, intravenous nivolumab 3 mg/kg every 2 weeks was associated with significantly better overall survival and progression-free survival and a significantly higher overall response rate than intravenous docetaxel in the second-line treatment of advanced, squamous NSCLC. Nivolumab was also better tolerated than docetaxel in CheckMate 017, and its adverse event profile (which included immune-mediated adverse events) was manageable. In conclusion, nivolumab represents an important advance in previously-treated, advanced, squamous NSCLC.
An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. [2018]Nivolumab is a programmed cell death 1 (PD-1) inhibitor that has been approved for treatment of advanced melanoma, non-small cell lung carcinoma, renal cell carcinoma and classical Hodgkin's lymphoma.
Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer. In this review we will summarize the data for efficacy and toxicity for these two agents. We conclude that they represent two valuable but interchangeable alternatives to target their approved indications. We will discuss how this can help global payers seeking to contain the cost of cancer therapeutics that continues to spiral out of control.
FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. [2018]On November 23, 2015, the FDA approved nivolumab (OPDIVO; Bristol-Myers Squibb) as a single agent for the first-line treatment of patients with BRAFV600 wild-type, unresectable or metastatic melanoma. An international, double-blind, randomized (1:1) trial conducted outside of the United States allocated 418 patients to receive nivolumab 3 mg/kg intravenously every 2 weeks (n = 210) or dacarbazine 1,000 mg/m2 intravenously every 3 weeks (n = 208). Patients with disease progression who met protocol-specified criteria (∼25% of each trial arm) were permitted to continue with the assigned treatment in a blinded fashion until further disease progression is documented. Overall survival was statistically significantly improved in the nivolumab arm compared with the dacarbazine arm [hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.30-0.60; P < 0.0001]. Progression-free survival was also statistically significantly improved in the nivolumab arm (HR, 0.43; 95% CI, 0.34-0.56; P < 0.0001). The most common adverse reactions (≥20%) of nivolumab were fatigue, diarrhea, constipation, nausea, musculoskeletal pain, rash, and pruritus. Nivolumab demonstrated a favorable benefit-risk profile compared with dacarbazine, supporting regular approval; however, it remains unclear whether treatment beyond disease progression contributes to the overall clinical benefit of nivolumab. Clin Cancer Res; 23(14); 3479-83. ©2017 AACR.
The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]Nivolumab is the human programmed cell death-1 (PD-1)-blocking antibody showing significant effect in many refractory cancers. However, little is known about its risks of hematological toxicities, rare but clinically serious and potentially life-threatening adverse events. We want to explore whether nivolumab can increase the risks of hematological toxicities compared with other immunotherapy or chemotherapy drugs.
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]Nivolumab is an immune checkpoint inhibitor specific to the programmed death 1 (PD-1) receptor. Nivolumab has shown clinical responses in many malignancies. Although immune-related adverse events (irAEs) associated with nivolumab are largely tolerable, severe irAEs have occurred in some patients. However, the mechanisms underlying the development of irAEs are not fully clarified.
Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? [2022]Nivolumab is a human immunoglobulin G4 monoclonal antibody that inhibits programmed cell death-1 activity by binding to the programmed cell death-1 receptors. Cancer cells express increased number of programmed cell death-1 ligands and this allows them to escape the cytotoxic effects of the T cells. Therefore, the negative programmed cell death-1 receptor signal regulates T-cell proliferation and activation is disrupted. However, this change in the activity of the T cells can cause them to lose their ability to recognize host cells. The immune response enabled by these agents has led to side effects, commonly known as "immune-related adverse events."
Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]The programmed death (PD)-1 immune checkpoint inhibitor nivolumab (Opdivo(®)) is approved in the USA for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have progression on or after platinum-based chemotherapy and in the EU for the treatment of adults with locally advanced or metastatic NSCLC after prior chemotherapy. In previously-treated patients with advanced nonsquamous NSCLC, overall survival was significantly prolonged and the overall response rate was significantly higher in patients who received intravenous nivolumab 3 mg/kg every 2 weeks versus intravenous docetaxel in the pivotal CheckMate 057 trial. Progression-free survival did not significantly differ between patients receiving nivolumab and those receiving docetaxel. Intravenous nivolumab had a manageable adverse event profile (including immune-mediated adverse events) and was better tolerated than docetaxel in the CheckMate 057 trial. Thus, nivolumab is an important new option for use in previously-treated patients with advanced nonsquamous NSCLC.
U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. [2023]On December 22, 2014, the FDA granted accelerated approval to nivolumab (OPDIVO; Bristol-Myers Squibb) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on a clinically meaningful, durable objective response rate (ORR) in a non-comparative analysis of 120 patients who received 3 mg/kg of nivolumab intravenously every 2 weeks with at least 6-month follow-up in an ongoing, randomized, open-label, active-controlled clinical trial. The ORR as assessed by a blinded independent review committee per RECIST v1.1 was 31.7% (95% confidence interval, 23.5-40.8). Ongoing responses were observed in 87% of responding patients, ranging from 2.6+ to 10+ months. In 13 patients, the response duration was 6 months or longer. The risks of nivolumab, including clinically significant immune-mediated adverse reactions (imARs), were assessed in 268 patients who received at least one dose of nivolumab. The FDA review considered whether the ORR and durations of responses were reasonably likely to predict clinical benefit, the adequacy of the safety database, and systematic approaches to the identification, description, and patient management for imARs in product labeling. Clin Cancer Res; 23(14); 3484-8. ©2017 AACR.