Safety and Preliminary Efficacy of BNA035 in Patients With Advanced Solid Tumors

NCT05150457 | Unknown Phase 1

• 1 other identifier: BNA035-101
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of the study is to evaluate the safety and tolerability of BNA035 in order to determine the maximum tolerated dose (MTD) and Recommended Phase 2 dose (RP2D) and to evaluate the preliminary efficacy for each combination regimen.

Conditions

Refractory Solid Tumors

Keywords

Cancer; Advanced cancer; Recurrent cancer; Solid tumor; Metastatic cancer; Refractory cancer

Outcome Measures

Primary Outcomes (2)

• Determination of the Maximum Tolerated Dose (MTD) Recommended Phase 2 Dose (RP2D) of BNA035 in patients with advanced solid tumors.

  Evaluated by the number of dose-limiting toxicities (DLT) graded using NCI CTCAE v 5.0

  From first dose of BNA035 (Cycle 1 Day 1) through the end of the DLT period (28 days from Cycle 1 Day 1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  To examine the incidence of clinical and laboratory adverse events after multiple doses of BNA035 in the dose escalation and dose expansion phases.

  From first dose of BNA035 through 90 days after the last BNA035 dose)

Secondary Outcomes (4)

• Peak Plasma Concentration of BNA035

  Days 1, 2, 3, 5, and 8 of Cycle 1 and 2; Day 15 of Cycle 1; Day 1 of Cycles 3, 4, and 5 (each cycle is 28 days); after last BNA035 treatment (up to 1 year)

• Area under the plasma concentration of BNA035

  Days 1, 2, 3, 5, and 8 of Cycle 1 and 2; Day 15 of Cycle 1; Day 1 of Cycles 3, 4, and 5 (each cycle is 28 days); after last BNA035 treatment (up to 1 year)

• Half-life of BNA035

  Days 1, 2, 3, 5, and 8 of Cycle 1 and 2; Day 15 of Cycle 1; Day 1 of Cycles 3, 4, and 5 (each cycle is 28 days); after last BNA035 treatment (up to 1 year)

• Investigate immunogenicity of BNA035

  Day 1 of Cycle 1; Day 1 of every other Cycle thereafter (each cycle is 28 days); after last BNA035 treatment (up to 1 year)

Study Arms (6)

Dose Escalation Phase, Dose Level 1

EXPERIMENTAL

Starting dose level of BNA035 administered as an IV infusion once weekly in 28 day cycles. Drug: BNA035 Administered once weekly as an IV infusion at the assigned dose level in 28 day cycles

Drug: BNA035

Dose Escalation Phase, Dose Level 2

EXPERIMENTAL

3 times the starting dose level of BNA035 administered as an IV infusion once weekly in 28 day cycles Drug: BNA035 Administered once weekly as an IV infusion at the assigned dose level in 28 day cycles

Drug: BNA035

Dose Escalation Phase, Dose Level 3

EXPERIMENTAL

10 times the starting dose level of BNA035 administered as an IV infusion once weekly in 28 day cycles Drug: BNA035 Administered once weekly as an IV infusion at the assigned dose level in 28 day cycles

Drug: BNA035

Dose Escalation Phase, Dose Level 4

EXPERIMENTAL

30 times the starting dose level of BNA035 administered as an IV infusion once weekly in 28 day cycles Drug: BNA035 Administered once weekly as an IV infusion at the assigned dose level in 28 day cycles

Drug: BNA035

Dose Escalation Phase, Dose Level 5

EXPERIMENTAL

100 times the starting dose level of BNA035 administered as an IV infusion once weekly in 28 day cycles Drug: BNA035 Administered once weekly as an IV infusion at the assigned dose level in 28 day cycles

Drug: BNA035

Dose Escalation Phase, Dose Level 6

EXPERIMENTAL

200 times the starting dose level of BNA035 administered as an IV infusion once weekly in 28 day cycles Drug: BNA035 Administered once weekly as an IV infusion at the assigned dose level in 28 day cycles

Drug: BNA035

Interventions

BNA035 DRUG

Anti-epidermal growth factor receptor (Anti-EGFR) and anti-cluster of differentiation 137 (anti-CD137) bispecific antibody

Dose Escalation Phase, Dose Level 1; Dose Escalation Phase, Dose Level 2; Dose Escalation Phase, Dose Level 3; Dose Escalation Phase, Dose Level 4; Dose Escalation Phase, Dose Level 5; Dose Escalation Phase, Dose Level 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following criteria to be eligible for enrollment in this study:
• Male or female ≥ 18 years of age.
• Histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of all standard therapy or for which no standard therapy is available.
• Measurable disease as per RECIST 1.1, or per Response Assessment in Neuro-Oncology (RANO) criteria for patients with glioblastoma multiforme and documented by computed tomography (CT) and/or magnetic resonance imaging (MRI).
• All persisting toxic effects of any prior anti-tumor therapy resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 Grade ≤ 1 or baseline before the first dose of study drug (with the exception of alopecia \[Grade 1 or 2 permitted\] and neurotoxicity \[Grade 1 or 2 permitted\]).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Life expectancy of ≥ 3 months, in the opinion of the Investigator.
• Adequate organ function defined as follows:
• Hematologic: Platelets ≥ 100 x 109/L; Hemoglobin ≥ 9.0 g/dL; Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (without blood transfusion, platelet transfusion, or growth factors within previous 7 days of the hematologic laboratory values obtained at Screening visit).
• Hepatic: Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN.
• Renal: Creatinine clearance (CLcr) ≥ 45 mL/min as calculated by the Cockcroft Gault method.
• Coagulation: Patients on full-dose oral anticoagulation, except warfarin, which is an excluded medication, must be on a stable dose (minimum duration 14 days). Patients on low molecular weight heparin will be allowed.
• Negative serum pregnancy test for female patients.
• If of childbearing potential, female patients must be willing to use highly effective double contraceptive measures starting with the Screening visit through 90 days after the last dose of study treatment.
• Double contraception is defined as a condom AND one other form of the following:

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from this study:
• Pregnant or lactating or planning to become pregnant (self or partner) at any time during the study, including the Follow-up Period.
• History or evidence of clinically significant disorder, condition, or disease that, in the opinion of the Investigator or Medical Monitor, would pose a risk to patient safety or interfere with the study evaluations, procedures, or completion.
• History of ≥ Grade 3 AEs during prior treatment with an immune checkpoint inhibitor, or history of discontinuation of treatment with an immune checkpoint inhibitor due to AEs. Previous Grade 3 immune-related adverse events (irAEs) if not considered by the Investigator to increase the patient's risk for investigational product (IP) related AEs, may be approved on a case-by-case basis in discussion with the Sponsor (e.g., hypothyroidism on stable thyroxine replacement, adrenal insufficiency on stable hormone replacement therapy, diabetes on stable insulin therapy).
• Active or history of prior autoimmune disease with the exception of:
• Hashimoto's Thyroiditis on stable thyroid replacement therapy;
• Type 1 Diabetes Mellitus (T1DM) on stable insulin therapy;
• Other prior autoimmune disorders not considered to put at higher risk for irAEs, based on Investigator judgment and approved by the Sponsor on a case-by-case basis (e.g., rheumatoid arthritis).
• The use of stable and controlled low dose steroids is acceptable.
• Patients with hepatocellular carcinoma are excluded.
• Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection requiring systemic therapy, active or chronic bleeding event within 28 days prior to first dose of study drug, or psychiatric illness/social situation that would limit compliance with study requirements as judged by the treating physician.
• Current or previous interstitial lung disease.
• Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification \> Class II), unstable angina, serious uncontrolled cardiac arrhythmia, cerebral vascular accident, coronary/peripheral artery bypass graft surgery, or pulmonary embolism within the last 6 months of first dose of study drug. Patients with small pulmonary embolism not thought to put patients at higher risks of AEs may be allowed on a case-by-case basis in discussion with the Sponsor.
• Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy) within 28 days of the first dose of study drug.
• Symptomatic with uncontrolled ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including thoracentesis or paracentesis), with no need for repeating paracentesis/thoracentesis within 7 days prior to Cycle 1 Day 1 (C1D1), is eligible.

Sponsors & Collaborators

• Binacea Pharma, Inc.: lead

Study Sites (3)

St George Private Hospital

Kogarah, New South Wales, 2217, Australia

RECRUITING

Pindara Private Hospital

Benowa, Queensland, 4217, Australia

RECRUITING

St. Vincents Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

RECRUITING

MeSH Terms

Conditions

Neoplasms; Recurrence; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Study Officials

• Josh Xiao, PhD

  Binacea Pharma, Inc.

  STUDY CHAIR

Central Study Contacts

Josh Xiao, PhD

CONTACT

+1-650-773-8722; josh_xiao@binaceapharma.com

Edgar Bautista, BSc

CONTACT

+1-3108679063; edgar_bautista@binaceapharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None (open label)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential Assignment

Study Record Dates

• First Submitted: November 11, 2021
• First Posted: December 9, 2021
• Study Start: February 8, 2022
• Primary Completion: November 1, 2023
• Study Completion: November 1, 2025
• Last Updated: September 27, 2022

Record last verified: 2022-09

Locations

AU (3)