HFB200301 + 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: Steroids, Immunosuppressants, CYP450 substrates

Disqualifiers: Autoimmune disease, Uncontrolled diabetes, others

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

Compensation: Varies

Number of Visits: 4

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety and tolerability of a new treatment, HFB200301, for individuals with advanced cancers. Researchers will evaluate the drug both alone and in combination with another drug, tislelizumab (an immunotherapy). Participants will help determine the optimal dose in the first phase and test its effectiveness in the second phase. The trial seeks individuals who have previously tried other treatments for their specific types of advanced cancer, such as gastric or lung cancer, without success. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot have had systemic anti-cancer therapy within 2 weeks before starting the study drug or within 4 weeks for immune-oncologic therapy. Also, you should not be on systemic steroid therapy greater than 10 mg/day of prednisone or equivalent within 14 days before the first dose.

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

Research has shown that HFB200301, when used alone, is generally safe. Studies testing different doses found that patients with advanced solid tumors usually tolerate it well, with serious side effects being rare. Most people manage the treatment without major issues.

When combined with another drug, tislelizumab, the safety data remains promising. Tislelizumab has been studied in many patients and is generally considered safe. Common side effects include fatigue and low red blood cell counts, but these are usually manageable.

Overall, both treatments, whether used alone or together, appear safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about HFB200301, especially when combined with Tislelizumab, because it represents a novel approach to treating advanced cancers. Unlike standard treatments like chemotherapy, which can affect both cancerous and healthy cells, HFB200301 is designed to specifically target cancer cells, potentially reducing side effects. Additionally, Tislelizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination aims to enhance the body's natural defenses while directly attacking the cancer, offering hope for improved outcomes for patients with advanced cancers.

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

Research shows that HFB200301 targets a protein called TNFR2, which aids the growth of certain tumors. Early results suggest this might help shrink tumors, particularly in cancers like head and neck squamous cell carcinoma. In this trial, some participants will receive HFB200301 alone, while others will receive it with tislelizumab, a treatment that enhances the immune system's ability to fight cancer. Studies have shown that this combination is effective and safe for treating solid tumors. This combination aims to boost the body's defense against cancer. Although more information is needed, these early signs suggest it could be promising for treating advanced cancers. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors like lung, kidney, or skin cancer who've had certain treatments already can join. They need to be well enough for daily activities and able to provide tumor samples. Excluded are those with severe lung conditions, recent major surgery, immune suppressive therapy, unstable health issues, or allergies related to the study drugs.

Inclusion Criteria

I have received at least one treatment for sarcoma.

I have had at least two treatments for my cervical cancer.

I have had at least two treatments for my testicular cancer.

Exclusion Criteria

Persisting toxicity of ≥Grade 2 (≥Grade 1 for diarrhea) relating to prior anti cancer therapy with the following exceptions: All grades of alopecia are acceptable, Endocrine dysfunction on replacement therapy is acceptable, Severe or unstable medical condition, including uncontrolled diabetes, coagulopathy, or unstable psychiatric condition, Major surgery within 4 weeks of the first dose of study drug, History or presence of drug or non-drug induced interstitial lung disease or pneumonitis ≥Grade 2. For combination only: non-small cell lung cancer patients, mesothelioma or patients with significantly impaired pulmonary function or who require supplemental oxygen at baseline must undergo an assessment of pulmonary function at screening, History of allergic reactions, immune related reactions, or cytokine release syndrome (CRS) attributed to compounds of similar chemical or biologic composition to monoclonal antibodies or any excipient of HFB200301, Using sensitive substrates of major cytochrome P450 (CYP450) enzymes, Known active malignancy, with the exception of the specific cancer under investigation in this trial, that required treatment within the previous 2 years

I have had immune therapy for my soft tissue sarcoma or testicular cancer.

I haven't taken high-dose steroids or immune suppressants in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HFB200301 as a monotherapy or in combination with tislelizumab during dose escalation and expansion phases

16 weeks

4 visits (in-person) per cycle, each cycle is 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HFB200301
• Tislelizumab

Trial Overview The trial is testing HFB200301 alone and combined with Tislelizumab in two parts: first finding a safe dose (escalation) then giving that dose to more people based on their cancer type (expansion). It aims to see how patients tolerate these treatments.

How Is the Trial Designed?

Group I: Dose Expansion - HFB200301 monotherapy Experimental Treatment 1 Intervention

Participants will be administered HFB200301 at monotherapy RDE as an intravenous infusion.

Group II: Dose Expansion - HFB200301 in combination with tislelizumab Experimental Treatment 2 Interventions

Participations will be administered HFB200301 in combination with tislelizumab at combination RDE as an intravenous infusion.

Group III: Dose Escalation - HFB200301 monotherapy Experimental Treatment 1 Intervention

Participants will be administered HFB200301 at dose levels 1-5 as an intravenous infusion to determine the Recommended Dose for Expansion (RDE).

Group IV: Dose Escalation - HFB200301 in combination with tislelizumab Experimental Treatment 2 Interventions

Participants will be administered HFB200301 at dose levels 1-4 in combination with one dose level of tislelizumab as an intravenous infusion to determine the combination Recommended Dose for Expansion (RDE).

Who Is Running the Clinical Trial?

HiFiBiO Therapeutics

Lead Sponsor

Trials

5

Recruited

380+

Published Research Related to This Trial

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]

In a phase 3 trial involving 332 patients with advanced nonsquamous non-small cell lung cancer (nsq-NSCLC), the combination of tislelizumab and chemotherapy significantly improved progression-free survival (PFS) compared to chemotherapy alone, with a median PFS of 9.7 months versus 7.6 months.

The addition of tislelizumab also resulted in higher response rates and longer duration of response, making it a promising first-line treatment option for patients with advanced nsq-NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. Lu, S., Wang, J., Yu, Y., et al.[2021]

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 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]

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 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]

Tislelizumab, an anti-PD-1 monoclonal antibody, showed a confirmed objective response rate of 24% in patients with PD-L1-positive urothelial carcinoma who had progressed after platinum therapy, indicating its efficacy in this challenging patient population.

The treatment had a manageable safety profile, with the most common adverse events being anemia (27%) and pyrexia (19%), and only a small percentage of patients experiencing severe side effects, suggesting that tislelizumab is a viable option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. Ye, D., Liu, J., Zhou, A., et al.[2022]

Tislelizumab, an anti-PD-1 monoclonal antibody, shows improved progression-free survival and objective response rates in treating non-small cell lung cancer (NSCLC), especially when combined with chemotherapy, based on a review of four randomized controlled trials involving 1565 patients.

While tislelizumab is generally effective, it is associated with treatment-emergent adverse events, including significant hematologic issues and immune-mediated effects like hypothyroidism and pneumonitis, with a mortality rate from these events ranging from 3.2% to 4.2%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials. Daei Sorkhabi, A., ZareDini, M., Fazlollahi, A., 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]

Citations

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NCT05238883 | A Study of HFB200301 as a Single Agent ... The purpose of this study is to test the safety and tolerability of HFB200301 as a single agent and in combination with tislelizumab in patients with ...

2. kidneycancer.org kidneycancer.org/trial/a-study-of-hfb200301-as-a-single-agent-and-in-combination-with-tislelizumab-in-adult-patients-with-advanced-solid-tumors/

A Study of HFB200301 as a Single Agent and in ... The purpose of this study is to test the safety and tolerability of HFB200301 as a single agent and in combination with tislelizumab in patients with advanced ...

3. clinicaltrial.be clinicaltrial.be/en/details/32807?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Study of HFB200301 as a Single Agent ... Participations will be administered HFB200301 in combination with tislelizumab at combination RDE as an intravenous infusion. Interventions:Drug ...

4. 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.

5. hifibio.com hifibio.com/wp-content/uploads/2024/09/HFB200301-ESMO-2024-Poster.pdf

Model-informed dose optimization of HFB200301, a ... HFB200301 Q2W dosing showed a favorable safety profile similar to that of Q4W dosing. • Additionally, Q2W dosing demonstrated preliminary ...

6. trials.braintumor.org trials.braintumor.org/trials/NCT05238883

A Study of HFB200301 as a Single Agent and in Combination With ... The purpose of this study is to test the safety and tolerability of HFB200301 ... advanced cancers. There are two parts in this ... safety data. Phase 3: Studies ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS2670

Phase I study of HFB200301, a first-in-class TNFR2 agonist ... The following cancer indications have been identified based on the prevalence of a TNFR2 high/CD8 high signature: Epstein-Barr Virus positive ( ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02589-4/fulltext

1011P Model-informed dose optimization of HFB200301, a ... Model-optimized dosing of HFB200301 may provide improved therapeutic activity while maintaining a favorable safety profile in pts with advanced solid tumors.

9. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/metastatic-melanoma

Metastatic Melanoma Clinical Trials The purpose of this study is to test the safety and tolerability of HFB200301 in patients with advanced cancers. There are two parts in this study. During ...