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 19, 2023
• Sponsor: HiFiBiO Therapeutics
• Information provided by (Responsible Party): HiFiBiO Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: HFB200301; Drug: Tislelizumab	Phase 1

Detailed Description:

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

1. A Screening Period of up to 28 days
2. A Treatment Period during which participants will receive the study drug on the first day of each cycle where each cycle is 28 days. Number of cycles depends on how the disease responds to the study drug
3. A Follow-up Period which involves 1 visit for single agent and 2 visits for combination.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 170 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 10, 2022
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

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 Name: 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 Name: BGB-A317

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events (AEs), serious AEs (SAEs), dose-limiting toxicities (DLTs), changes in laboratory values, vital signs, electrocardiogram (ECG), and tolerability (dose interruptions, reductions, and dose intensity) [ Time Frame: Cycle 1 Day 1 to 30 days after the last dose of study drug(s) (each cycle is 28 days), assessed up to 3 years ]
2. 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 study drug(s) (each cycle is 28 days), assessed up to 3 years ]

Secondary Outcome Measures :

1. 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 study drug(s) (each cycle is 28 days), assessed up to 3 years ]
2. Disease Control Rate (DCR) as determined by (m)RECIST 1.1 and iRECIST [ Time Frame: Baseline to 30 days after the last dose of study drug(s) (each cycle is 28 days), assessed up to 3 years ]
3. 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 ]
4. 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 ]
5. Minimum serum concentration (Cmin) [ Time Frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 28 days), through study completion, an average of 3 year ]
6. Maximum serum concentration (Cmax) [ Time Frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 28 days), through study completion, an average of 3 year ]
7. Area under the concentration versus time curve (AUC) [ Time Frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 28 days), through study completion, an average of 3 year ]
8. Terminal half-life (T1/2) [ Time Frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 28 days), through study completion, an average of 3 year ]
9. Serum concentration for measurement of anti-HFB200301 antibodies [ Time Frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 28 days), through study completion, an average of 3 year ]
10. To assess the pharmacodynamic (PD) effects of HFB200301 as a single agent and in combination 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

Other Outcome Measures:

1. 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) ]
2. 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) ]
3. AUC vs percent change in tumor size [ Time Frame: Cycle 1 Day 1 to Cycle 4 Day 1 (each cycle is 28 days) ]
4. 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) ]
5. 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) ]

Eligibility Criteria

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

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

Contacts and Locations

Contacts

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

Locations

United States, Arizona

Mayo Clinic; Recruiting

Scottsdale, Arizona, United States, 85259

United States, California

USC/Norris Comprehensive Cancer Center; Recruiting

Los Angeles, California, United States, 90033

United States, Florida

Mayo Clinic; Recruiting

Jacksonville, Florida, United States, 32224

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University School of Medicine; Recruiting

Saint Louis, Missouri, United States, 63110

United States, Texas

The University of Texas, MD Anderson Cancer Center; Terminated

Houston, Texas, United States, 77030

United States, Virginia

NEXT Virginia Cancer Specialists; Recruiting

Fairfax, Virginia, United States, 22031

Spain

Hospital Universitario Vall d'Hebron; Recruiting

Barcelona, Spain, 08035

Hospital Universitario 12 de Octubre; Recruiting

Madrid, Spain, 28041

Hospital Clinico Universitario de Valencia; Recruiting

Valencia, Spain, 46010

Sponsors and Collaborators

HiFiBiO Therapeutics

More Information

• Responsible Party: HiFiBiO Therapeutics
• ClinicalTrials.gov Identifier: NCT05238883
• Other Study ID Numbers: HFB-200301-01; 2021-006231-25 ( EudraCT Number )
• First Posted: February 14, 2022
• Last Update Posted: May 19, 2023
• Last Verified: May 2023

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

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Mesothelioma; Neoplasms, Germ Cell and Embryonal; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma, Squamous Cell; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenoma; Neoplasms, Mesothelial; Head and Neck Neoplasms; Tislelizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents