Clinical trial NCT05238883: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: 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
Lead sponsor: HiFiBiO Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-02-14
Enrollment: 170
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 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

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.

Primary outcomes:
measure: Number of participants with adverse events (AEs), serious AEs (SAEs), dose-limiting toxicities (DLTs), and tolerability (dose interruptions, reductions, and dose intensity)
timeFrame: assessed up to 3 years
measure: To determine a Recommended Phase 2 Dose (RP2D) during Dose Expansion
timeFrame: assessed up to 3 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: assessed up to 3 years
measure: Disease Control Rate (DCR)
timeFrame: assessed up to 3 years
measure: Duration of Response (DOR)
timeFrame: assessed up to 3 years
measure: Progression Free Survival (PFS)
timeFrame: assessed up to 3 years
measure: Maximum serum concentration (Cmax)
timeFrame: average of 3 years
measure: Terminal half-life (T1/2)
timeFrame: average of 3 years
measure: Area under the concentration versus time curve (AUC)
timeFrame: average of 3 years
measure: Serum concentration for measurement of anti-HFB200301 antibodies
timeFrame: average of 3 years
measure: To assess the pharmacodynamic (PD) effects of HFB200301 as a single agent and in combination
timeFrame: average of 3 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Houston
country: United States
facility: The University of Texas, MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia Cancer Specialists
state: Virginia
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
References: