HFB200603 + Tislelizumab for Advanced Cancers

Not currently recruiting at 10 trial locations

Overseen By Edward Steele, Clinical Trial Manager

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: HiFiBiO Therapeutics

Must not be taking: Systemic steroids, Immune suppressants

Disqualifiers: Autoimmune diseases, Uncontrolled diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment, HFB200603 (an experimental treatment), both alone and with another drug called tislelizumab (an immunotherapy), for advanced cancers. Initially, the trial will explore different doses to determine a safe amount, then apply that dose to various cancer types. Suitable participants have advanced cancers, such as renal cell carcinoma or non-small cell lung cancer, and have already tried several other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that HFB200603 is generally safe and well-tolerated, both alone and with the drug tislelizumab. Tislelizumab has undergone testing in various cancer types and is usually considered safe. Common side effects include fatigue and anemia, or low red blood cell levels. Although serious risks can occur, they are less common.

This trial tests both HFB200603 and tislelizumab to determine the optimal dose. As an early phase trial, the primary focus is on safety. Participants will have their health closely monitored to assess how their bodies respond to the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about HFB200603 and Tislelizumab for advanced cancers because they offer a novel approach compared to standard treatments like chemotherapy and traditional immunotherapies. HFB200603 is unique due to its potential to enhance immune system activity specifically against cancer cells, which could lead to more targeted and effective treatment. Tislelizumab, an anti-PD-1 antibody, works to unleash the immune system by preventing cancer cells from hiding, potentially leading to better outcomes. Together, these treatments may offer a promising new mechanism with the potential for improved effectiveness and reduced side effects compared to existing options.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research shows that HFB200603 could be a promising treatment for advanced cancers. In earlier studies, 46% of patients with advanced solid tumors experienced tumor shrinkage or halted growth when treated with HFB200603. Nearly half of the participants saw positive changes in their tumors. In this trial, some participants will receive HFB200603 as monotherapy, while others will receive it combined with tislelizumab. Combining HFB200603 with tislelizumab aims to enhance the body's immune response against tumors. Tislelizumab alone has proven effective and safe for various solid tumors. Together, these treatments might offer a strong approach to fighting advanced cancers. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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.

You have a tumor that can be measured using specific guidelines called RECIST 1.1.

I can have a biopsy before and during treatment.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• HFB200603
• Tislelizumab

Trial Overview

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.

How Is the Trial Designed?

Group I: Dose Expansion - HFB200603 monotherapy (optional) Experimental Treatment 1 Intervention

Participants will be administered HFB200603 at monotherapy RDE as an intravenous infusion.

Group II: Dose Expansion - HFB200603 in combination with tislelizumab Experimental Treatment 2 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 monotherapy Experimental Treatment 1 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 tislelizumab Experimental Treatment 2 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).

Who Is Running the Clinical Trial?

HiFiBiO Therapeutics

Lead Sponsor

Trials

5

Recruited

380+

Published Research Related to This Trial

In a phase 2 study involving 249 patients with previously treated advanced hepatocellular carcinoma (HCC), tislelizumab showed an objective response rate of 13%, indicating its potential effectiveness as a treatment option.

The treatment was generally well-tolerated, with only 15% of patients experiencing grade ≥3 treatment-related adverse events, and no deaths attributed to the treatment, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial. Ren, Z., Ducreux, M., Abou-Alfa, GK., et al.[2023]

In a study of 115 patients with recurrent or metastatic cervical cancer treated with tislelizumab, the overall response rate was 39.1%, and the median progression-free survival was 19.6 months, indicating promising antitumor activity.

Baseline serum C-reactive protein (CRP) levels and the CRP-to-albumin ratio (CAR) were identified as independent risk factors for predicting the efficacy and prognosis of tislelizumab treatment, with higher levels associated with shorter progression-free and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers. Zheng, X., Gu, H., Cao, X., et al.[2023]

In a phase II study with 70 patients suffering from relapsed/refractory classical Hodgkin lymphoma, tislelizumab showed a high overall response rate of 87.1% and a complete response rate of 67.1% after a median follow-up of 33.8 months, indicating its efficacy as a treatment option.

The treatment demonstrated a favorable safety profile, with 97.1% of patients experiencing treatment-related adverse events, but only 31.4% having severe (grade ≥3) events, and just 8.6% discontinuing treatment due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. Song, Y., Gao, Q., Zhang, H., et al.[2023]

Tislelizumab is a modified PD-1 antibody that effectively inhibits tumor growth in various cancers, including Hodgkin's lymphoma and lung cancer, and has received multiple approvals in China for its use.

It has a favorable safety profile with common side effects like fatigue and anemia, and it offers economic advantages over other PD-1 inhibitors, making it a promising option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. Zhang, L., Geng, Z., Hao, B., et al.[2023]

Tislelizumab is an anti-PD-1 monoclonal antibody developed as an immunotherapy for cancer, specifically approved in December 2019 in China for relapsed or refractory classical Hodgkin's lymphoma after at least two prior chemotherapy treatments.

The drug has shown promise in treating both hematological cancers and advanced solid tumors, indicating its potential for future approvals in additional cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: First Approval. Lee, A., Keam, SJ.[2020]

Tislelizumab, an anti-PD-1 monoclonal antibody, shows promising efficacy and a manageable safety profile in treating advanced non-small cell lung cancer (NSCLC), with higher affinity to PD-1 compared to other similar therapies like pembrolizumab and nivolumab.

The drug's unique design minimizes binding to macrophages, potentially reducing resistance to treatment, and ongoing trials are exploring its effectiveness in combination with other therapies, which could enhance its role in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab: an investigational anti-PD-1 antibody for the treatment of advanced non-small cell lung cancer (NSCLC). Liu, SY., Wu, YL.[2022]

Tislelizumab, a PD-1 inhibitor, significantly improved the overall response rate (ORR) and disease control rate (DCR) in patients with malignant solid tumors, with odds ratios of 2.59 and 1.78, respectively, based on a meta-analysis of seven phase III trials involving 3478 participants.

The treatment also demonstrated improved overall survival (OS) and progression-free survival (PFS), with hazard ratios of 0.71 and 0.68, indicating that tislelizumab is an effective option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tislelizumab for malignant solid tumor: a systematic review and meta-analysis of phase III randomized trials. Abushanab, AK., Mustafa, MT., Mousa, MT., et al.[2023]

An indirect comparison of tislelizumab and pembrolizumab in combination with chemotherapy for advanced NSCLC, involving over 2,000 participants from 6 randomized trials, showed no significant differences in overall survival, progression-free survival, or objective response rates between the two treatments.

Both treatments were associated with a similar risk of severe adverse events, indicating that either tislelizumab or pembrolizumab can be considered effective and safe options for first-line therapy in advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Guo, Y., Jia, J., Hao, Z., et al.[2023]

Citations

1.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)02584-5/fulltext

1006P Phase I dose escalation study of HFB200603, a ...

This Phase I trial assesses the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of HFB200603 in pts with advanced refractory ...

2.

hifibio.com

hifibio.com/wp-content/uploads/2024/09/HFB200603-ESMO-2024-Poster.pdf

Phase I Dose Escalation Study of HFB200603, a Best-in- ...

Here, we present data from an ongoing Phase I dose-escalation, multi-center trial evaluating HFB200603 both as a monotherapy and in combination ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05789069

NCT05789069 | A Study of HFB200603 as a Single Agent ...

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 ...

4.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)02584-5/pdf

1006P Phase I dose escalation study of HFB200603, a ...

Here, we present initial data, including safety, efficacy, pharmaco- kinetics, and pharmacodynamics, for BI 1703880 plus ezabenlimab (anti-PD-1 anti- body) in ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10860318/

From glioma gloom to immune bloom: unveiling novel ...

This tandem approach has exhibited early clinical activity, boasting an overall response rate of 46% in cases of advanced solid tumors [115].

6.

trials.braintumor.org

trials.braintumor.org/trials/NCT05789069

A Study of HFB200603 as a Single Agent and in Combination ...

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 ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12265466/

Long-term safety analysis of pooled data for tislelizumab as ...

Tislelizumab, an anti-programmed cell death protein 1 monoclonal antibody, has demonstrated efficacy and safety in solid tumors.

8.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40578840/

Long-term safety analysis of pooled data for tislelizumab as ...

Tislelizumab's safety profile, as monotherapy or combined with chemotherapy, remains consistent with previous reports across tumor types.

9.

withpower.com

withpower.com/trial/phase-1-carcinoma-renal-cell-2-2023-2f2b9

HFB200603 + Tislelizumab for Advanced Cancers

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 ...

10.

cancer.gov

cancer.gov/research/participate/clinical-trials/intervention/anti-btla-monoclonal-antibody-hfb200603

Clinical Trials Using Anti-BTLA Monoclonal Antibody ...

A Study of HFB200603 as a Single Agent and in Combination With Tislelizumab in Adult Patients With Advanced Solid Tumors. Status: Active. Location: See ...