BI-1808 + Pembrolizumab for Advanced Cancer
Recruiting in Palo Alto (17 mi)
+15 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: BioInvent International AB
Must be taking: Anti-PD-1 therapy
Must not be taking: Immunosuppressants, Chemotherapy
Disqualifiers: CNS metastases, Autoimmune disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The goal of this first in human clinical trial is to test BI-1808 administered as single agent and in combination with pembrolizumab in subjects with advanced malignancies whose disease has progressed after standard therapy.
The main questions it aims to answer are:
* how safe and tolerable is BI-1808
* what is maximum tolerated or administrated dose
* to determine recommended dose for further clinical trials. Participants will receive infusions of BI-1808 alone or combination with pembrolizumab every 3 weeks.
For the purpose of this study, subjects with advanced malignancies includes subjects with advanced solid tumors and subjects with T-cell lymphoma (TCL),
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, it mentions that you should not have received chemotherapy, immunotherapy, or certain other treatments within a few weeks before starting the trial. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug pembrolizumab in treating advanced cancer?
Pembrolizumab has been shown to improve survival in patients with advanced non-small cell lung cancer and melanoma, as it helps the immune system attack cancer cells more effectively. Studies have demonstrated that patients receiving pembrolizumab had better outcomes compared to those receiving traditional chemotherapy.
12345Is the combination of BI-1808 and Pembrolizumab safe for humans?
Pembrolizumab (also known as KEYTRUDA or MK-3475) has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and more serious immune-related issues like pneumonitis (lung inflammation) and thyroid problems. While specific safety data for BI-1808 is not provided, pembrolizumab's safety profile is well-documented in other cancer treatments.
12678What makes the drug BI-1808 + Pembrolizumab unique for advanced cancer?
The combination of BI-1808 and Pembrolizumab is unique because it combines a new treatment (BI-1808) with Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells. Pembrolizumab has shown effectiveness in various cancers, and this combination may offer a novel approach for advanced cancer by potentially enhancing the immune response.
124910Eligibility Criteria
Adults over 18 with advanced malignancies, including solid tumors and specific types of cutaneous T-cell lymphoma (CTCL), who have not responded to standard cancer treatments. Participants must be able to provide consent, have a life expectancy of at least 12 weeks, an ECOG performance status of 0-1, and measurable disease lesions. Specific criteria apply for NSCLC and OC patients regarding prior therapies.Inclusion Criteria
I am over 18, agree to participate in the trial, and have a confirmed advanced cancer diagnosis.
I have a tumor that can be measured and biopsied safely.
My cancer has high PD-L1 and I've had anti-PD-1 therapy.
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Phase 1 Part A - Dose Escalation
Dose escalation of BI-1808 as a single agent to evaluate safety and tolerability and to determine the recommended Phase 2 dose (RP2D) as a single agent
Up to 104 weeks
Every 3 weeks
Phase 1 Part B - Dose Escalation
Dose escalation of BI-1808 in combination with pembrolizumab to evaluate safety and tolerability and to determine the recommended Phase 2 dose (RP2D) for the combination
Up to 104 weeks
Every 3 weeks
Phase 2a Part A - Dose Expansion
BI-1808 administered as a single agent at the hypothesized recommended Phase 2 dose determined in Phase 1
Up to 104 weeks
Every 3 weeks
Phase 2a Part B - Dose Expansion
BI-1808 administered in combination with pembrolizumab at the respective hypothesized recommended Phase 2 doses determined in Phase 1
Up to 104 weeks
Every 3 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 2 years and 90 days
Participant Groups
The trial is testing BI-1808 alone and combined with Pembrolizumab in patients whose cancers have progressed after standard therapy. It's a multi-phase study assessing the safety and efficacy of these drugs in treating various advanced malignancies.
4Treatment groups
Experimental Treatment
Group I: Phase I, Part B - Dose escalation and Safety of BI-1808 in combination with pembrolizumabExperimental Treatment2 Interventions
Dose escalation of BI-1808 in combination with pembrolizumab.
Group II: Phase I, Part A - Dose escalation and safety of BI-1808 as single agentExperimental Treatment1 Intervention
Dose escalation of BI-1808 administrated a single agent
Group III: Phase 2a, Part B - Dose expansion of BI-1808 in combination with pembrolizumabExperimental Treatment2 Interventions
BI-1808 administered in combination with pembrolizumab at the respective hypothesized recommended phase 2 doses determined in Phase 1
Group IV: Phase 2a - Part A dose expansion of BI-1808 as a single agentExperimental Treatment1 Intervention
BI-1808 administered as a single agent at the hypothesized recommended phase 2 dose determined in Phase 1
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope National Medical CenterDuarte, CA
University of PennsylvaniaPhiladelphia, PA
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Who Is Running the Clinical Trial?
BioInvent International ABLead Sponsor
Merck Sharp & Dohme LLCIndustry 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.
Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. [2022]In the randomized, open-label, phase III KEYNOTE-024 study, pembrolizumab significantly improved progression-free survival and overall survival (OS) compared with platinum-based chemotherapy in patients with previously untreated advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 tumor proportion score of 50% or greater and without EGFR/ALK aberrations. We report an updated OS and tolerability analysis, including analyses adjusting for potential bias introduced by crossover from chemotherapy to pembrolizumab.
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.Approval was based on two randomized, open-label, active-controlled trials demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE-024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41-0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37-0.68; p < .001). In KEYNOTE-010, patients with disease progression on or after platinum-containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58-0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49-0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.
Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). [2022]Interim analyses of the phase 3 KEYNOTE-006 study showed superior overall and progression-free survival of pembrolizumab versus ipilimumab in patients with advanced melanoma. We present the final protocol-specified survival analysis.
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.
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).
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.
New Approved Use for Keytruda. [2022]Pembrolizumab (Keytruda) is now approved as a single agent to treat advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient in those whose disease has progressed following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation.