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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Sarcoma; Renal Cell Carcinoma; Cervical Cancer; Testicular Germ Cell Tumor; Gastric Cancer; Non Small Cell Lung Cancer; Mesothelioma; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: HFB200301; Drug: Tislelizumab

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
• Enrollment (Estimated): 170
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Emily Lefkovitz, Clinical Trial Manager; Phone Number: +1(513)579-9911; Email: e.lefkovitz@Medpace.com

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 De Octubre
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clínico Universitario de Valencia
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC/Norris Comprehensive Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • Texas
    • Houston, Texas, United States, 77030
      • Terminated
      • The University of Texas, MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	Drug: HFB200301; Participants will be administered HFB200301 as described in the experimental arm.
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).	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 Names: BGB-A317
Experimental: Dose Expansion - HFB200301 monotherapy; Participants will be administered HFB200301 at monotherapy RDE as an intravenous infusion.	Drug: HFB200301; Participants will be administered HFB200301 as described in the experimental arm.
Experimental: Dose Expansion - HFB200301 in combination with tislelizumab; Participations will be administered HFB200301 in combination with tislelizumab at combination RDE as an intravenous infusion.	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 Names: BGB-A317

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Time Frame
AUC vs percent of Tcell changes in the blood	Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days)
AUC vs percent of Tcell changes in the tumor	Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days)
AUC vs percent change in tumor size	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	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	Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: HiFiBiO Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 16, 2021
• First Submitted That Met QC Criteria: February 9, 2022
• First Posted (Actual): February 14, 2022

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Kidney Neoplasms; Adenoma; Carcinoma, Squamous Cell; Neoplasms, Mesothelial; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Neoplasms, Germ Cell and Embryonal; Carcinoma; Squamous Cell Carcinoma of Head and Neck; Mesothelioma; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tislelizumab
• Other Study ID Numbers: HFB-200301-01; 2021-006231-25 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No