A Study of HFB200603 as a Single Agent and in Combination With Tislelizumab in Adult Patients With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT05789069
• Recruitment Status: Recruiting
• First Posted: March 29, 2023
• Last Update Posted: December 4, 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 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.

Condition or disease	Intervention/treatment	Phase
Renal Cell Carcinoma; Melanoma; Non Small Cell Lung Cancer; Gastric Cancer; Colorectal Cancer	Drug: HFB200603; 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 21 days. Number of cycles depends on how the disease responds to the study drug
3. A Follow-up Period which involves 2 visits

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 83 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 HFB200603 (Anti-BTLA 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: May 9, 2023
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation - HFB200603 monotherapy; Participants will be administered HFB200603 at dose levels 1-4 as an intravenous infusion to determine the Recommended Dose for Expansion (RDE).	Drug: HFB200603; Participants will be administered HFB200603 as described in the experimental arm.
Experimental: Dose Escalation - HFB200603 in combination with tislelizumab; 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).	Drug: HFB200603; Participants will be administered HFB200603 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 - HFB200603 monotherapy (optional); Participants will be administered HFB200603 at monotherapy RDE as an intravenous infusion.	Drug: HFB200603; Participants will be administered HFB200603 as described in the experimental arm.
Experimental: Dose Expansion - HFB200603 in combination with tislelizumab; 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.	Drug: HFB200603; Participants will be administered HFB200603 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) meeting protocol-defined Dose-Limiting Toxicity (DLT) criteria during Dose Escalation [ Time Frame: The first cycle of treatment (Day 1 up to Day 21) ]
   Severity of adverse events will be based on common terminology criteria for adverse events (CTCAE) version 5.0
2. Number of participants with AEs [ Time Frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years ]
   Severity of AEs will be assessed based on CTCAE version 5.0 (except for cytokine release syndrome which will be assessed by American Society for Transplantation and Cellular Therapy grading)
3. Number of participants with changes in laboratory values [ Time Frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years ]
4. Number of participants with changes in vital signs [ Time Frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years ]
5. Number of participants with changes in electrocardiogram (ECG) [ Time Frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years ]
6. Number of participants with changes in tolerability (dose interruptions and dose intensity) [ Time Frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years ]
7. To determine a Recommended Phase 2 Dose (RP2D) during Dose Expansion [ Time Frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years ]

Secondary Outcome Measures :

1. Objective Response Rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-RECIST (iRECIST) [ Time Frame: Baseline to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years ]
2. Disease Control Rate (DCR) as determined by RECIST 1.1 and iRECIST [ Time Frame: Baseline to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years ]
3. Duration of Response (DOR) as determined by 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 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 21 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 21 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 21 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 21 days), through study completion, an average of 3 year ]
9. Serum concentration for measurement of anti-HFB200603 antibodies [ Time Frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 21 days), through study completion, an average of 3 year ]

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:

• Patient must have one of the following cancers and previously received the following lines of systemic therapy for the advanced/metastatic disease:

  • Renal cell carcinoma: at least 2 lines of therapy
  • Non-small cell lung cancer: at least 2 lines of therapy

  • Melanoma:

    • BRAF V600E positive: must have received at least 2 lines of therapy
    • BRAF V600E negative: must have received at least 1 line of therapy
  • Gastric cancer: at least 1 line of therapy
  • Colorectal cancer: at least 3 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
• 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 cytotoxic agents with major delayed toxicity (e.g., mitomycin C), 6 weeks of washout are mandated.
• Therapeutic radiation therapy within the past 2 weeks
• Active autoimmune diseases or history of autoimmune disease that may relapse
• Any malignancy ≤ 5 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively
• Systemic steroid therapy (>10 mg/day of prednisone or equivalent) or any immune suppressive medication ≤ 14 days before first dose
• Patients with toxicities (as a result of prior anticancer therapy) which have not recovered to baseline or stabilized, except for adverse events not considered a likely safety risk (e.g., alopecia, neuropathy, and specific laboratory abnormalities)
• Severe or unstable medical condition, including uncontrolled diabetes, coagulopathy, or unstable psychiatric condition
• Major surgery within 28 days of the first dose of study drug
• History of interstitial lung disease, non-infectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis or acute lung diseases. For combination only: non-small cell lung cancer patients, 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 HFB200603 or tislelizumab
• 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: Edward Steele, Clinical Trial Manager; (513)579-9911; e.steele@medpace.com

Locations

United States, California

USC Norris Comprehensive Cancer Center; Recruiting

Los Angeles, California, United States, 90033

United States, Pennsylvania

Fox Chase Cancer Center; Recruiting

Philadelphia, Pennsylvania, United States, 19111

United States, Virginia

New Experimental Therapeutics of Virginia - NEXT Oncology; Recruiting

Fairfax, Virginia, United States, 22031

Italy

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale; Recruiting

Napoli, Italy, 80131

UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore; Recruiting

Rome, Italy, 00168

Centro Ricerche Cliniche di Verona s.r.l.; Recruiting

Verona, Italy, 37134

Spain

Clinica Universidad de Navarra - Madrid; Recruiting

Madrid, Spain, 28027

South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz; Recruiting

Madrid, Spain, 28040

South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC; Recruiting

Madrid, Spain, 28050

Clinica Universidad de Navarra - Pamplona; Recruiting

Pamplona, Spain, 31008

Hospital Clinico Universitario de Valencia; Recruiting

Valencia, Spain, 46010

Sponsors and Collaborators

HiFiBiO Therapeutics

More Information

• Responsible Party: HiFiBiO Therapeutics
• ClinicalTrials.gov Identifier: NCT05789069
• Other Study ID Numbers: HFB-200603-01
• First Posted: March 29, 2023
• Last Update Posted: December 4, 2023
• Last Verified: November 2023

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

Additional relevant MeSH terms:

Carcinoma, Renal Cell; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Tislelizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents