BNT314 +/- Immune Checkpoint Inhibitor for Cancer
Recruiting in Palo Alto (17 mi)
+13 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: BioNTech SE
Must not be taking: Corticosteroids, Immunosuppressants, others
Disqualifiers: Infection, Heart failure, Hypertension, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests the safety and effectiveness of a new drug, BNT314, alone and with pembrolizumab, in patients with advanced cancers who lack other treatment options. BNT314 aims to attack cancer cells directly, while pembrolizumab boosts the immune system's ability to fight cancer. Pembrolizumab has been shown to improve recurrence-free survival in various cancers and is approved for multiple indications.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you have taken certain treatments like anticancer agents or investigational drugs within a specific time frame before starting the trial. It's best to discuss your current medications with the study team to see if they might affect your eligibility.
What data supports the effectiveness of the drug Pembrolizumab in cancer treatment?
Pembrolizumab, a drug that helps the immune system fight cancer, has shown effectiveness in treating advanced melanoma and certain types of lung cancer. It works by blocking a protein that prevents the immune system from attacking cancer cells, and has been approved for use in these conditions.
12345What safety information is available for BNT314 and Pembrolizumab (Keytruda)?
Pembrolizumab (Keytruda) has been associated with some side effects, including fatigue, cough, nausea, and more serious immune-related effects like pneumonitis (lung inflammation), colitis (inflammation of the colon), and rare cases of type 1 diabetes. These side effects occur in a small percentage of patients and are generally outweighed by the benefits in treating certain cancers.
12367What makes the drug BNT314 with Pembrolizumab unique for cancer treatment?
BNT314 combined with Pembrolizumab is unique because it targets the PD-1/PD-L1 pathway, enhancing the immune system's ability to fight cancer by blocking a mechanism that tumors use to hide from immune cells. Pembrolizumab, a part of this combination, is already known for its effectiveness in treating various cancers by boosting T-cell activity, making this combination potentially more effective in engaging the immune system against cancer.
128910Eligibility Criteria
Adults over 18 with advanced solid tumors that have worsened after standard treatment or who can't tolerate such treatments. They must be able to consent, follow study procedures, and have a life expectancy of more than 3 months. Good physical condition (ECOG score of 0 or 1) and proper organ function are required. Women must test negative for pregnancy and agree to contraception; men also need to use contraception.Inclusion Criteria
Have measurable disease according to RECIST v1.1
Have adequate coagulation function at screening
My blood tests show my bone marrow is working well.
+15 more
Exclusion Criteria
Prolonged QTc interval at baseline of ≥470 milliseconds using Fridericia's QT correction formula
Known alcohol dependency within 6 months enrollment in this study
Planned enrollment in another study of an IMP, starting after Visit D1 and continuously until the last planned visit in this study
+23 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Patients receive escalating dose levels of BNT314 to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD).
Variable, until MTD/MAD is determined
Safety Run-In (SRI)
BNT314 is combined with pembrolizumab to test safety in a small group of participants.
Variable, until safety is confirmed
Expansion
BNT314 combined with pembrolizumab is administered to a larger group of participants to further assess safety and efficacy.
Up to 2 years
Follow-up
Participants are monitored for safety and effectiveness after treatment.
Up to 3 years after first dose
Participant Groups
The trial is testing BNT314's safety alone and combined with pembrolizumab in cancer patients. It has three parts: dose escalation to find the safest high dose, a safety run-in combining both drugs in a small group, followed by an expansion phase treating up to 199 patients with this combination.
2Treatment groups
Experimental Treatment
Group I: BNT314 MonotherapyExperimental Treatment1 Intervention
Escalating dose levels and backfill cohorts
Group II: BNT314 + pembrolizumabExperimental Treatment2 Interventions
The BNT314 starting dose for the SRI combination therapy will be one DL lower than the RP2D/MTD/maximum administered dose (MAD) determined from the monotherapy dose escalation.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
START MidwestGrand Rapids, MI
Cleveland ClinicCleveland, OH
Carolina BioOncology Institute, LLCHuntersville, NC
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Who Is Running the Clinical Trial?
BioNTech SELead Sponsor
GenmabIndustry Sponsor
References
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.
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.
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
Pembrolizumab: first global approval. [2021]Pembrolizumab [Keytruda(®) (US)], a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of cancer. Pembrolizumab has received its first global approval for the treatment of advanced, unresectable or metastatic malignant melanoma in the US, for use in patients with disease progression after prior treatment with ipilimumab and, for BRAF V600 mutation-positive patients, a BRAF inhibitor. It is the first anti-PD-1 therapy to receive regulatory approval in the US, and is currently under regulatory review in the EU. This article summarizes the milestones in the development of pembrolizumab leading to this first approval for the treatment of malignant melanoma.
Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.
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).
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.
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.
Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for the treatment of advanced melanoma and pretreated non-small-cell lung cancer (NSCLC).
Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. [2023]PD-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer (NK)/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers.