HFB200603 + Tislelizumab for Advanced Cancers

Recruiting at 8 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

83 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{1 2 4 5 6}

What 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. ^{1 2 3 7 8}

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.

Eligibility 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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Tislelizumab: First Approval. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. [2023]

4. England 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

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

6. Switzerland 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. [2023]

7. Switzerland 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. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers. [2023]