Clinical trial NCT05789069: A Study of HFB200603 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 HFB200603 (Anti-BTLA Antibody) as a Single Agent and in Combination With Tislelizumab (Anti-PD-1 Antibody) in Adult Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Renal Cell Carcinoma
Melanoma
Non Small Cell Lung Cancer
Gastric Cancer
Colorectal Cancer
Lead sponsor: HiFiBiO Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-03-29
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Eligibility 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

Primary outcomes:
measure: Number of participants with adverse events (AEs) meeting protocol-defined Dose-Limiting Toxicity (DLT) criteria during Dose Escalation
timeFrame: The first cycle of treatment (Day 1 up to Day 21)
measure: Number of participants with AEs
timeFrame: 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
measure: Number of participants with changes in laboratory values
timeFrame: 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
measure: Number of participants with changes in vital signs
timeFrame: 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
measure: Number of participants with changes in electrocardiogram (ECG)
timeFrame: 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
measure: Number of participants with changes in tolerability (dose interruptions and dose intensity)
timeFrame: 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
measure: To determine a Recommended Phase 2 Dose (RP2D) during Dose Expansion
timeFrame: 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 outcomes:
measure: Objective Response Rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-RECIST (iRECIST)
timeFrame: Baseline to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years
measure: Disease Control Rate (DCR) as determined by RECIST 1.1 and iRECIST
timeFrame: Baseline to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years
measure: Duration of Response (DOR) as determined by RECIST 1.1 and iRECIST
timeFrame: Start of first response to first date of disease progression, clinical progression or death, whichever occurs first, assessed up to 3 years
measure: Progression Free Survival (PFS) as determined by RECIST 1.1 and iRECIST
timeFrame: Baseline to disease progression or death, whichever occurs first, assessed up to 3 years
measure: Minimum serum concentration (Cmin)
timeFrame: 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
measure: Maximum serum concentration (Cmax)
timeFrame: 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
measure: Area under the concentration versus time curve (AUC)
timeFrame: 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
measure: Terminal half-life (T1/2)
timeFrame: 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
measure: Serum concentration for measurement of anti-HFB200603 antibodies
timeFrame: 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
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Fairfax
country: United States
facility: New Experimental Therapeutics of Virginia - NEXT Oncology
state: Virginia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
city: Rome
country: Italy
facility: UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
city: Verona
country: Italy
facility: Centro Ricerche Cliniche di Verona s.r.l.
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid
city: Madrid
country: Spain
facility: South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
References: