Colorectal Cancer, Gastric Cancer, Melanoma, Non Small Cell Lung Cancer, Renal Cell Carcinoma
Conditions
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
Interventions
DRUGHFB200603
Participants will be administered HFB200603 as described in the experimental arm.
DRUGTislelizumab
Participants will be administered tislelizumab as described in the experimental arm.
Sponsors
HiFiBiO Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) meeting protocol-defined Dose-Limiting Toxicity (DLT) criteria during Dose Escalation | 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 |
| Number of participants with AEs | 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) |
| Number of participants with changes in laboratory values | 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 | — |
| Number of participants with changes in vital signs | 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 | — |
| Number of participants with changes in electrocardiogram (ECG) | 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 | — |
| Number of participants with changes in tolerability (dose interruptions and dose intensity) | 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 | — |
| To determine a Recommended Phase 2 Dose (RP2D) during Dose Expansion | 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
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-RECIST (iRECIST) | Baseline to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years |
| Disease Control Rate (DCR) as determined by RECIST 1.1 and iRECIST | Baseline to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years |
| Duration of Response (DOR) as determined by RECIST 1.1 and iRECIST | Start of first response to first date of disease progression, clinical progression or death, whichever occurs first, assessed up to 3 years |
| Progression Free Survival (PFS) as determined by RECIST 1.1 and iRECIST | Baseline to disease progression or death, whichever occurs first, assessed up to 3 years |
| Minimum serum concentration (Cmin) | 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 |
| Maximum serum concentration (Cmax) | 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 |
| Area under the concentration versus time curve (AUC) | 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 |
| Terminal half-life (T1/2) | 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 |
| Serum concentration for measurement of anti-HFB200603 antibodies | 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 |
Countries
Italy, Spain, United States
Outcome results
None listed