A Study of HFB200301 as a Single Agent and in Combination With Tislelizumab in Adult Patients With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT05238883
• Recruitment Status: Recruiting
• First Posted: February 14, 2022
• Last Update Posted: May 1, 2024
• Sponsor: HiFiBiO Therapeutics
• Information provided by (Responsible Party): HiFiBiO Therapeutics

Tracking Information

• First Submitted Date: December 16, 2021
• First Posted Date: February 14, 2022
• Last Update Posted Date: May 1, 2024
• Actual Study Start Date: March 10, 2022
• Estimated Primary Completion Date: December 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 14, 2023)

• Number of participants with adverse events (AEs), serious AEs (SAEs), dose-limiting toxicities (DLTs), and tolerability (dose interruptions, reductions, and dose intensity) [ Time Frame: assessed up to 3 years ]
• To determine a Recommended Phase 2 Dose (RP2D) during Dose Expansion [ Time Frame: assessed up to 3 years ]

Original Primary Outcome Measures (submitted: February 9, 2022)

• Number of participants with adverse events (AEs), serious AEs (SAEs), dose-limiting toxicities (DLTs), changes in laboratory values, vital signs and electrocardiogram (ECG) [ Time Frame: Cycle 1 Day 1 to 30 days after the last dose of HFB200301 (each cycle is 28 days), assessed up to 3 years ]
• To determine a Recommended Phase 2 Dose (RP2D) during Dose Expansion [ Time Frame: Cycle 1 Day 1 to 30 days after the last dose of HFB200301 (each cycle is 28 days), assessed up to 3 years ]

Current Secondary Outcome Measures (submitted: December 14, 2023)

• Objective Response Rate (ORR) [ Time Frame: assessed up to 3 years ]
• Disease Control Rate (DCR) [ Time Frame: assessed up to 3 years ]
• Duration of Response (DOR) [ Time Frame: assessed up to 3 years ]
• Progression Free Survival (PFS) [ Time Frame: assessed up to 3 years ]
• Maximum serum concentration (Cmax) [ Time Frame: average of 3 years ]
• Terminal half-life (T1/2) [ Time Frame: average of 3 years ]
• Area under the concentration versus time curve (AUC) [ Time Frame: average of 3 years ]
• Serum concentration for measurement of anti-HFB200301 antibodies [ Time Frame: average of 3 years ]
• To assess the pharmacodynamic (PD) effects of HFB200301 as a single agent and in combination [ Time Frame: average of 3 years ]
  Percent change in immunologic changes to immune cells

Original Secondary Outcome Measures (submitted: February 9, 2022)

• Objective Response Rate (ORR) as determined by (modified) Response Evaluation Criteria in Solid Tumors [(m)RECIST] 1.1 and immune-RECIST (iRECIST) [ Time Frame: Baseline to 30 days after the last dose of HFB200301 (each cycle is 28 days), assessed up to 3 years ]
• Disease Control Rate (DCR) as determined by (m)RECIST 1.1 and iRECIST [ Time Frame: Baseline to 30 days after the last dose of HFB200301 (each cycle is 28 days), assessed up to 3 years ]
• Duration of Response (DOR) as determined by (m)RECIST 1.1 and iRECIST [ Time Frame: Start of first response to first date of disease progression, clinical progression or death, whichever occurs first, assessed up to 3 years ]
• Progression Free Survival (PFS) as determined by (m)RECIST 1.1 and iRECIST [ Time Frame: Baseline to disease progression or death, whichever occurs first, assessed up to 3 years ]
• Minimum serum concentration (Cmin) [ Time Frame: Cycle 1 Day 1 to day of the last dose of HFB200301 (each cycle is 28 days), through study completion, an average of 3 year ]
• Maximum serum concentration (Cmax) [ Time Frame: Cycle 1 Day 1 to day of the last dose of HFB200301 (each cycle is 28 days), through study completion, an average of 3 year ]
• Area under the concentration versus time curve (AUC) [ Time Frame: Cycle 1 Day 1 to day of the last dose of HFB200301 (each cycle is 28 days), through study completion, an average of 3 year ]
• Terminal half-life (T1/2) [ Time Frame: Cycle 1 Day 1 to day of the last dose of HFB200301 (each cycle is 28 days), through study completion, an average of 3 year ]
• Serum concentration for measurement of anti-HFB200301 antibodies [ Time Frame: Cycle 1 Day 1 to day of the last dose of HFB200301 (each cycle is 28 days), through study completion, an average of 3 year ]
• To assess the pharmacodynamic (PD) effects of HFB200301 in the blood and in the tumor [ Time Frame: Cycle 1 Day 1 to Cycle 3 Day 2 (each cycle is 28 days) ]
  Percent change in immunologic changes to immune cells in the blood and tumor

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: February 9, 2022)

• AUC vs percent of Tcell changes in the blood [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]
• AUC vs percent of Tcell changes in the tumor [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]
• AUC vs percent change in tumor size [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]
• Percent Tcell changes in the blood vs percent change in tumor size [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]
• Percent Tcell changes in the tumor vs percent change in tumor size [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]

Descriptive Information

• Brief Title: A Study of HFB200301 as a Single Agent and in Combination With Tislelizumab in Adult Patients With Advanced Solid Tumors
• Official Title: A Phase 1a/1b, Open-Label, Multi-Center, Dose Escalation and Expansion Study of HFB200301 (TNFR2 Agonist Antibody) as a Single Agent and in Combination With Tislelizumab (Anti-PD-1 Antibody) in Adult Patients With Advanced Solid Tumors
• Brief Summary: 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 cancers. There are two parts in this study. During the escalation part, groups of participants will receive increasing doses of HFB200301 as a monotherapy or in combination with tislelizumab until a safe and tolerable dose of HFB200301 as a single agent or combination therapy is determined. During the expansion part, participants will take the dose of HFB200301 as a monotherapy or in combination with tislelizumab that was determined from the escalation part of the study and will be assigned to a group based on the type of cancer the participants have.

Detailed Description

This is a Phase 1a/1b, first in human, open-label, dose escalation and expansion study in adults with advanced cancers. The study will comprise of

1. A Screening Period
2. A Treatment Period during which participants will receive the study drug on the first day of each cycle
3. A Follow-up Period

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Gastric Cancer
• Renal Cell Carcinoma
• Melanoma
• Sarcoma
• Testicular Germ Cell Tumor
• Cervical Cancer
• Mesothelioma
• Non Small Cell Lung Cancer
• Head and Neck Squamous Cell Carcinoma

Intervention

• Drug: HFB200301
  Participants will be administered HFB200301 as described in the experimental arm.
• Drug: Tislelizumab
  Participants will be administered tislelizumab as described in the experimental arm.
  Other Name: BGB-A317

Study Arms

• Experimental: Dose Escalation - HFB200301 monotherapy
  Participants will be administered HFB200301 at dose levels 1-5 as an intravenous infusion to determine the Recommended Dose for Expansion (RDE).
  Intervention: Drug: HFB200301
• Experimental: Dose Escalation - HFB200301 in combination with tislelizumab
  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).
  Interventions:

  • Drug: HFB200301
  • Drug: Tislelizumab
• Experimental: Dose Expansion - HFB200301 monotherapy
  Participants will be administered HFB200301 at monotherapy RDE as an intravenous infusion.
  Intervention: Drug: HFB200301
• Experimental: Dose Expansion - HFB200301 in combination with tislelizumab
  Participations will be administered HFB200301 in combination with tislelizumab at combination RDE as an intravenous infusion.
  Interventions:

  • Drug: HFB200301
  • Drug: Tislelizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 22, 2022): 170
• Original Estimated Enrollment (submitted: February 9, 2022): 90
• Estimated Study Completion Date: December 2026
• Estimated Primary Completion Date: December 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Previously received the following lines of systemic therapy for the advanced/metastatic disease:

  • Gastric cancer: at least 2 lines of therapy
  • Renal cell carcinoma: at least 2 lines of therapy

  • Melanoma:

    • BRAF V600E mutant: must have received at least 2 lines of therapy
    • BRAF V600E wild type: must have received at least 1 line of therapy
  • Sarcoma: at least 1 line of therapy
  • Testicular germ cell tumor: at least 2 lines of therapy
  • Cervical cancer: at least 2 lines of therapy
  • Mesothelioma: at least 2 lines of therapy
  • Non-small cell lung cancer: at least 2 lines of therapy
  • Head and neck squamous cell carcinoma: at least 2 lines of therapy
• Suitable site to biopsy at pre-treatment and on-treatment
• Measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST (mRECIST) for mesothelioma
• Eastern Cooperative Oncology Group performance status of 0 or 1

Exclusion Criteria:

• Systemic anti-cancer therapy within 2 weeks prior to start of study drug or within 4 weeks for immune-oncologic therapy
• For soft tissue sarcoma and testicular germ cell tumor patients only: prior immune therapy
• Therapeutic radiation therapy within the past 2 weeks
• Prior exposure to agents targeting the Tumor Necrosis Factor Receptor type 2 (TNFR2) receptor
• Active autoimmune disease requiring systemic treatment in the previous 2 years
• Systemic steroid therapy (>10 mg/day of prednisone or equivalent) or any immune suppressive therapy ≤ 14 days before first dose

• 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

• For combination only:

  • Prior randomization in a tislelizumab study regardless of the treatment arm, until the primary and key secondary endpoints of the study have read out
  • Hypersensitivity to tislelizumab or any of its excipients.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Emily Lefkovitz, Clinical Trial Manager; +1(513)579-9911; e.lefkovitz@Medpace.com

• Listed Location Countries: Spain, United States

Administrative Information

• NCT Number: NCT05238883
• Other Study ID Numbers: HFB-200301-01; 2021-006231-25 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: HiFiBiO Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: HiFiBiO Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: HiFiBiO Therapeutics
• Verification Date: April 2024