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

Study Overview
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Brief Summary
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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
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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 A Screening Period A Treatment Period during which participants will receive the study drug on the first day of each cycle A Follow-up Period

Official Title
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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

Conditions
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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

Intervention / Treatment
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* Drug: HFB200301
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation - HFB200301 monotherapy<br>Participants will be administered HFB200301 at dose levels 1-5 as an intravenous infusion to determine the Recommended Dose for Expansion (RDE). | Drug: HFB200301<br>* Participants will be administered HFB200301 as described in the experimental arm.<br>|
| Experimental: Dose Escalation - HFB200301 in combination with tislelizumab<br>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<br>* Participants will be administered HFB200301 as described in the experimental arm.<br>Drug: Tislelizumab<br>* Participants will be administered tislelizumab as described in the experimental arm.<br>* Other names: BGB-A317;|
| Experimental: Dose Expansion - HFB200301 monotherapy<br>Participants will be administered HFB200301 at monotherapy RDE as an intravenous infusion. | Drug: HFB200301<br>* Participants will be administered HFB200301 as described in the experimental arm.<br>|
| Experimental: Dose Expansion - HFB200301 in combination with tislelizumab<br>Participations will be administered HFB200301 in combination with tislelizumab at combination RDE as an intravenous infusion. | Drug: HFB200301<br>* Participants will be administered HFB200301 as described in the experimental arm.<br>Drug: Tislelizumab<br>* Participants will be administered tislelizumab as described in the experimental arm.<br>* Other names: BGB-A317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |