HFB200603 + Tislelizumab for Advanced Cancers
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: HiFiBiO Therapeutics
Must not be taking: Systemic steroids, Immune suppressants
Disqualifiers: Autoimmune diseases, Uncontrolled diabetes, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this study is to test the safety and tolerability of HFB200603 as a single agent and in combination with tislelizumab in patients with advanced cancers. There are two parts in this study. During the escalation part, groups of participants will receive increasing doses of HFB200603 as a monotherapy or in combination with tislelizumab until a safe and tolerable dose of HFB200603 as a single agent or combination therapy is determined. During the expansion part, participants will take the doses of HFB200603 as a monotherapy (optional arm) or in combination with tislelizumab that were determined from the escalation part of the study and will be assigned to a group based on the type of cancer the participants have.
Will I have to stop taking my current medications?
The trial requires that you stop taking any systemic anti-cancer therapy at least 2 weeks before starting the study drug, or 4 weeks for immune-oncologic therapy. If you are on cytotoxic agents with major delayed toxicity, a 6-week washout period is needed.
What data supports the effectiveness of the drug Tislelizumab for advanced cancers?
Tislelizumab has shown promising anti-tumor effects in various solid tumors, including lung, liver, and gastric cancers, and has been approved in China for several cancer types like Hodgkin's lymphoma and urothelial carcinoma. It has an acceptable safety profile and offers an economic advantage over other similar drugs.
12345Is the combination of HFB200603 and Tislelizumab safe for humans?
Tislelizumab has been studied in various cancers and is generally considered safe, with common side effects like fatigue and anemia, and more serious risks like respiratory infections and liver issues. It has been compared to other treatments and shows similar safety profiles.
12456What makes the drug HFB200603 + Tislelizumab unique for advanced cancers?
The drug combination of HFB200603 and Tislelizumab is unique because Tislelizumab is a modified antibody designed to block a protein called PD-1, which helps cancer cells hide from the immune system. This combination may offer a new approach for treating advanced cancers by enhancing the body's immune response against tumors.
12378Eligibility Criteria
Adults with certain advanced cancers (stomach, lung, colorectal, kidney cancer, melanoma) who've had specific prior treatments can join. They need a site for biopsy and measurable disease by RECIST 1.1 standards. A good performance status is required (0 or 1), and they must not have had recent cancer therapy or major surgery, no active autoimmune diseases or severe medical conditions.Inclusion Criteria
I am fully active or restricted in physically strenuous activity but can do light work.
I can have a biopsy before and during treatment.
You have a tumor that can be measured using specific guidelines called RECIST 1.1.
+1 more
Exclusion Criteria
I do not have severe diabetes, bleeding disorders, or uncontrolled mental health conditions.
My side effects from previous cancer treatments have mostly gone away or stabilized, except for things like hair loss or numbness.
You have a current autoimmune disease or a history of an autoimmune disease that could come back.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
4 weeks
Treatment - Dose Escalation
Participants receive increasing doses of HFB200603 as a monotherapy or in combination with tislelizumab to determine a safe and tolerable dose
Variable, each cycle is 3 weeks
1 visit per cycle (in-person)
Treatment - Dose Expansion
Participants receive HFB200603 as a monotherapy or in combination with tislelizumab at the recommended dose for expansion
Variable, each cycle is 3 weeks
1 visit per cycle (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 3 years
2 visits
Participant Groups
The trial tests HFB200603 alone and with Tislelizumab in two parts: dose-escalation to find safe levels and expansion where those doses are given based on the participant's cancer type. The goal is to determine safety and tolerability of these drugs in combination or as monotherapy.
4Treatment groups
Experimental Treatment
Group I: Dose Expansion - HFB200603 monotherapy (optional)Experimental Treatment1 Intervention
Participants will be administered HFB200603 at monotherapy RDE as an intravenous infusion.
Group II: Dose Expansion - HFB200603 in combination with tislelizumabExperimental Treatment2 Interventions
Participants will be administered HFB200603 in combination with tislelizumab at combination RDEs as an intravenous infusion. Based on the cancer type, participants will be randomized to combination HFB200603 RDE 1 or RDE 2.
Group III: Dose Escalation - HFB200603 monotherapyExperimental Treatment1 Intervention
Participants will be administered HFB200603 at dose levels 1-4 as an intravenous infusion to determine the Recommended Dose for Expansion (RDE).
Group IV: Dose Escalation - HFB200603 in combination with tislelizumabExperimental Treatment2 Interventions
Participants will be administered HFB200603 at dose levels 1-3 in combination with one dose level of tislelizumab as an intravenous infusion to determine the combination Recommended Doses for Expansion (RDEs).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fox Chase Cancer CenterPhiladelphia, PA
USC Norris Comprehensive Cancer CenterLos Angeles, CA
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Who Is Running the Clinical Trial?
HiFiBiO TherapeuticsLead Sponsor
References
Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. [2023]Tislelizumab is an anti-programmed death receptor 1 (PD-1) monoclonal immunoglobulin G 4 antibody developed by BeiGene. The structure of tislelizumab has been modified to maximally inhibit the binding of PD-1 to programmed death ligand 1 (PD-L1) and minimize the binding of tislelizumab to Fcγ receptors. In clinical studies, tislelizumab has shown preliminary anti-tumor effects in various solid tumors, such as Hodgkin's lymphoma, urothelial carcinoma, lung cancer, gastric and esophageal cancer, liver cancer, nasopharyngeal carcinoma, colorectal cancer, and microsatellite instability-high/mismatch repair-deficient tumors. In addition, it also showed new promise in solid tumor treatment in combination with ociperlimab. Due to its satisfactory anti-tumor effects, tislelizumab has received approvals in China for the treatment of classical Hodgkin's lymphoma, urothelial carcinoma, squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, and hepatocellular carcinoma, and it is now under investigation for a new indication in microsatellite instability-high/mismatch repair-deficient tumors. Moreover, it has been granted orphan designations in hepatocellular carcinoma, esophageal cancer, and gastric cancer, including cancer of the gastroesophageal junction, by the US Food and Drug Administration. Tislelizumab has an acceptable safety profile; the most common adverse effects include fatigue, anemia, and decreased neutrophil count, while the most fatal events have been related to respiratory infection or failure, and hepatic injury. Tislelizumab has an economic advantage compared with other well-studied PD-1/PD-L1 inhibitors; thus, the introduction of it could provide clinical oncologists with an effective weapon against tumors and may alleviate the burden of cancer patients.
Tislelizumab: First Approval. [2020]Tislelizumab (®;; Tileilizhu Dankang Zhusheye) is an anti-human programmed death receptor-1 (PD-1) monoclonal IgG4 antibody that is being developed by BeiGene as an immunotherapeutic, anti-neoplastic drug. Tislelizumab has been investigated in haematological cancers and advanced solid tumours, leading to its approval in December 2019 in China for patients with relapsed or refractory classical Hodgkin's lymphoma after at least second-line chemotherapy. This article summarises the major milestones in the development of tislelizumab for this first approval for classical Hodgkin's lymphoma, and its potential upcoming approvals in other indications.
Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. [2023]Tislelizumab is an anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody specifically designed to minimize binding to Fcγ receptors (FcγR).
Efficacy and safety of tislelizumab for malignant solid tumor: a systematic review and meta-analysis of phase III randomized trials. [2023]We aimed to describe the clinical efficacy and safety of tislelizumab, a new (PD-1) inhibitor, in patients with malignant solid tumors.
Tislelizumab: an investigational anti-PD-1 antibody for the treatment of advanced non-small cell lung cancer (NSCLC). [2022]Non-small cell lung cancer (NSCLC) accounts for most lung cancers worldwide and has a poor prognosis at later stages; programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have provided promising new treatment approaches for these patients. Tislelizumab, an anti-PD-1 monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Tislelizumab has demonstrated clinical activity and is approved in China for treatment of previously treated classical Hodgkin lymphoma and previously treated metastatic PD-L1-high urothelial carcinoma.
Tislelizumab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials. [2023]Purpose: Pembrolizumab and tislelizumab have demonstrated significant clinical benefits in first-line treatment for advanced NSCLC. However, no head-to-head clinical trial has ever compared the optimal choice. Therefore, we conducted an indirect comparison to explore the optimal choice for advanced NSCLC combined with chemotherapy. Methods: We conducted a systematic review of randomized trials; the clinical outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Indirect comparisons between tislelizumab and pembrolizumab were conducted with the Bucher method. Results: Data were abstracted from 6 randomized trials involving more than 2,000 participants. Direct meta-analysis showed that both treatment regimens improved clinical outcomes compared with chemotherapy alone (PFS: hazard ratio (HR)tis+chemo/chemo 0.55, 95% CI 0.45-0.67; HRpem+chemo/chemo 0.53, 95% CI 0.47-0.60; ORR: relative risk (RR)tis+chemo/chemo 1.50, 95% CI 1.32-1.71; RRpem+chemo/chemo 1.89, 95% CI 1.44-2.48). Regarding safety outcomes, tislelizumab and pembrolizumab have a higher risk in the incidence of grade 3 or higher AEs (RRtis+chemo/chemo 1.12, 95% CI 1.03-1.21; RRpem+chemo/chemo 1.13, 95% CI 1.03-1.24). The indirect comparison showed that there was no significant difference between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy in terms of PFS (HR: 1.04, 95% CI 0.82-1.31), ORR (RR: 0.79, 95% CI 0.59-1.07), the incidence of grade 3 or higher AEs (RR 0.99, 95% CI 0.87-1.12), and AEs leading to death (RR 0.70, 95% CI 0.23-2.09). In progression-free survival subgroup analysis, the results demonstrate no significant differences in PFS by PD-L1 TPS expression level, age, liver metastasis status, and smoking status between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy. Conclusion: The efficacy and safety of tislelizumab combination chemotherapy were not substantially different from pembrolizumab combination chemotherapy.
Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial. [2023]Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC.
Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers. [2023]Tislelizumab is an anti-programmed cell death 1 (PD-1) monoclonal antibody engineered to minimize binding to Fcγ receptors. It has been used to treat several solid tumors. However, its efficacy and toxicity, and the predictive and prognostic value of baseline hematological parameters in patients with recurrent or metastatic cervical cancer (R/M CC) receiving tislelizumab remain unclear.