A Study of BND-35 in Participants With Advanced Solid Tumors

NCT06274437 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BND-35-001
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 5

Brief Summary

This is an open-label, multicenter, dose escalation and dose optimization study designed to evaluate safety, tolerability and preliminary anti-tumor activity of BND-35 administered alone and in combination with nivolumab or with cetuximab. The study will enroll advanced cancer patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy. The study will be comprised of two parts - a dose escalation phase (Part 1) and a dose optimization (Part 2). Part 1 is comprised of three sub-parts: BND-35 administered alone (Sub-Part 1A), BND-35 administered in combination with nivolumab (Sub-Part 1B), and BND-35 administered in combination with cetuximab (Sub-Part 1C). Part 2 is composed of two sub-parts: a dose optimization part where up to two doses of BND-35 per indication are administered in combination with nivolumab or with cetuximab.

Conditions

Cancer

Outcome Measures

Primary Outcomes (5)

• Part 1: Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

  Adverse event (AE): any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of study drug, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent events were events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.

  Through study completion, up to approximately 34 months

• Part 1: Proportion of patients who discontinued study treatment due to TEAEs

  Number of patients who discontinued study treatment due to TEAEs

  Through study completion, up to approximately 34 months

• Part 1: Incidence of TEAEs dose limiting toxicities (DLT)

  Incidence of TEAEs meeting protocol defined DLT criteria

  Up to 21 days in Cycle 1

• Part 2: Objective Response Rate (ORR) per RECIST v1.1

  Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1

  Through study completion, up to approximately 24 months

• Part 2: Incidence of TEAEs and SAEs

  Adverse event (AE): any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of study drug, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent events were events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.

  Through study completion, an average of 24 months

Secondary Outcomes (16)

• Part 1: Objective Response Rate (ORR) per RECIST v1.1

  Through study completion, up to approximately 34 months

• Part 1: Maximum observed plasma concentration (Cmax)

  Through study completion, up to approximately 34 months

• Part 1: Serum concentration at the end of the dosing interval (Ctrough)

  Through study completion, up to approximately 34 months

• Part 1: Time of maximum observed serum concentration (Tmax)

  Through study completion, up to approximately 34 months

• Part 1: Terminal elimination half-life (T1/2)

  Through study completion, up to approximately 34 months

Study Arms (5)

BND-35 Dose Escalation (Sub-Part 1A)

EXPERIMENTAL

Accelerated titration followed by standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. BND-35 will be administered at escalating doses of 0.3 mg/kg to 20 mg/kg intravenously (IV), every 2 weeks (Q2W)

Drug: BND-35

BND-35 in Combination with Nivolumab Dose Escalation (Sub-Part 1B)

EXPERIMENTAL

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. BND-35 will be administered at escalating doses of 3 mg/kg to 20 mg/kg intravenously (IV) every 2 weeks (Q2W). Nivolumab will be administered at a dose of 240 mg IV, every 2 weeks (Q2W).

Drug: BND-35; Drug: Nivolumab

BND-35 in Combination with Cetuximab Dose Escalation (Sub-Part 1C)

EXPERIMENTAL

Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. BND-35 will be administered at escalating doses of 3 mg/kg to 20 mg/kg intravenously (IV) every 2 weeks (Q2W). Cetuximab will be administered intravenously (IV) at a dose of 500 mg/m2, every 2 weeks (Q2W)

Drug: BND-35; Drug: Cetuximab

BND-35 in Combination with Nivolumab Dose Optimization (Sub-Part 2A)

EXPERIMENTAL

BND-35 dose optimization in combination with nivolumab. The indications for the combination cohorts will be selected following completion of Part 1. Enrollment will start after the recommended dose(s) of BND-35 have been determined based on data from Sub-Parts 1A, 1B, and 1C. Nivolumab will be administered at a dose of 240 mg IV, every 2 weeks (Q2W).

Drug: BND-35; Drug: Nivolumab

BND-35 in Combination with Cetuximab Dose Optimization (Sub-Part 2B)

EXPERIMENTAL

BND-35 dose optimization in combination with cetuximab. The indications for the combination cohorts will be selected following completion of Part 1. Enrollment will start after the recommended dose(s) of BND-35 have been determined based on data from Sub-Parts 1A, 1B, and 1C. Cetuximab will be administered intravenously (IV) at a dose of 500 mg/m2, every 2 weeks (Q2W)

Drug: BND-35; Drug: Cetuximab

Interventions

BND-35 DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Also known as: Monoclonal antibody

BND-35 Dose Escalation (Sub-Part 1A); BND-35 in Combination with Cetuximab Dose Escalation (Sub-Part 1C); BND-35 in Combination with Cetuximab Dose Optimization (Sub-Part 2B); BND-35 in Combination with Nivolumab Dose Escalation (Sub-Part 1B); BND-35 in Combination with Nivolumab Dose Optimization (Sub-Part 2A)

Nivolumab DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Also known as: Opdivo

BND-35 in Combination with Nivolumab Dose Escalation (Sub-Part 1B); BND-35 in Combination with Nivolumab Dose Optimization (Sub-Part 2A)

Cetuximab DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Also known as: Erbitux

BND-35 in Combination with Cetuximab Dose Escalation (Sub-Part 1C); BND-35 in Combination with Cetuximab Dose Optimization (Sub-Part 2B)

Eligibility Criteria

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

You may qualify if:

• Patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy
• Histologic confirmation of malignancy
• Measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
• Participants must have adequate organ function as defined by laboratory tests
• Part 1: Following tumor types: Breast cancer, cholangiocarcinoma, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, melanoma, ovarian cancer, renal cell carcinoma, pancreatic adenocarcinoma, soft tissue sarcomas

You may not qualify if:

• Active, known or suspected autoimmune disease
• Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
• Brain or leptomeningeal metastases
• Known history of positive test for HIV or known AIDS
• Acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Participants after solid organ or allogeneic hematopoietic stem cell transplant
• History of life-threatening toxicity related to prior immune therapy
• History of life-threatening toxicity related to prior cetuximab or other anti-epidermal growth factor receptor antibodies (for Sub-Part 1C)
• Unstable or deteriorating cardiovascular disease within the previous 6 months
• Any major surgery within 4 weeks of study drug administration
• Prior immune therapy treatments, unless at least 4 weeks have elapsed from last dose
• Cytotoxic/Non-cytotoxic anti-cancer agents, unless at least 4 weeks have elapsed from last dose
• Use of other investigational drugs within 28 days
• Prior treatment with immunoglobulin-like transcripts (ILT3)-targeting agents
• Administration of a live attenuated vaccine within 28 days

Sponsors & Collaborators

• Biond Biologics: lead

Study Sites (5)

Rambam Health Care Campus

Haifa, 3109601, Israel

RECRUITING

Hadassah University Medical Center

Jerusalem, 91120, Israel

RECRUITING

Rabin Medical Center

Petah Tikva, 49100, Israel

RECRUITING

Sheba Medical Center

Ramat Gan, 52621, Israel

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

Antibodies, Monoclonal; Nivolumab; Cetuximab

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized

Study Officials

• Natalia Ashtamker

  Biond Bio

  STUDY DIRECTOR

Central Study Contacts

Natalia Ashtamker, MD

CONTACT

+972548886441; natalia@biondbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2024
• First Posted: February 23, 2024
• Study Start: June 2, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: August 7, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IL (5)