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

A Phase 1, Dose Escalation and Dose Optimization Study of the Safety, Tolerability, and Anti-tumor Activity of BND-35 Administered Alone and in Combination With Nivolumab or With Cetuximab in Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer
• Intervention / Treatment: Drug: Cetuximab; Drug: BND-35; Drug: Nivolumab

Detailed Description

Estimated Study Duration:

Dose Escalation (Part 1): Approximately 34 months. Dose Optimization/Expansion (Part 2): Approximately 24 months.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Natalia Ashtamker, MD; Phone Number: +972548886441; Email: natalia@biondbio.com

Study Locations

• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
    • Contact: Ruth Perets
    • Contact: Phone Number: +97247776234; Email: ru_perets@rambam.health.gov.il
  • Jerusalem, Israel, 91120
    • Hadassah University Medical Center
    • Contact: Jonathan Cohen
    • Contact: Phone Number: +97226776781; Email: cohenjon@hadassah.org.il
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
    • Contact: Solomon Shtemer
    • Contact: Phone Number: +97239378110; Email: shtemers@clalit.org.il
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
    • Contact: Gal Strauss; Phone Number: +97235304498; Email: gal.strauss@sheba.health.gov.il
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
    • Contact: Ravit Geva; Phone Number: +97236973193; Email: ravitg@tlvmc.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BND-35 Dose Escalation (Sub-Part 1A); 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; Pharmaceutical form: Solution for infusion; Route of administration: Intravenous; Other Names: Monoclonal antibody
Experimental: BND-35 in Combination with Nivolumab Dose Escalation (Sub-Part 1B); 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; Pharmaceutical form: Solution for infusion; Route of administration: Intravenous; Other Names: Monoclonal antibody; Drug: Nivolumab; Pharmaceutical form: Solution for infusion; Route of administration: Intravenous; Other Names: Opdivo
Experimental: BND-35 in Combination with Cetuximab Dose Escalation (Sub-Part 1C); 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: Cetuximab; Pharmaceutical form: Solution for infusion; Route of administration: Intravenous; Other Names: Erbitux; Drug: BND-35; Pharmaceutical form: Solution for infusion; Route of administration: Intravenous; Other Names: Monoclonal antibody
Experimental: BND-35 in Combination with Nivolumab Dose Optimization (Sub-Part 2A); 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; Pharmaceutical form: Solution for infusion; Route of administration: Intravenous; Other Names: Monoclonal antibody; Drug: Nivolumab; Pharmaceutical form: Solution for infusion; Route of administration: Intravenous; Other Names: Opdivo
Experimental: BND-35 in Combination with Cetuximab Dose Optimization (Sub-Part 2B); 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: Cetuximab; Pharmaceutical form: Solution for infusion; Route of administration: Intravenous; Other Names: Erbitux; Drug: BND-35; Pharmaceutical form: Solution for infusion; Route of administration: Intravenous; Other Names: Monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: 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 34 months
Part 1: Maximum observed plasma concentration (Cmax)	Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.	Through study completion, up to approximately 34 months
Part 1: Serum concentration at the end of the dosing interval (Ctrough)	Ctrough is the lowest concentration of drug reached before the next dose was administered.	Through study completion, up to approximately 34 months
Part 1: Time of maximum observed serum concentration (Tmax)	Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.	Through study completion, up to approximately 34 months
Part 1: Terminal elimination half-life (T1/2)	Terminal half-life is the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination.	Through study completion, up to approximately 34 months
Part 1: Area under the plasma concentration-time curve (AUC)	AUC is the area under the concentration-time curve of drug	Through study completion, up to approximately 34 months
Part 1: Incidence of anti-drug antibodies (ADA)	Number of participants with ADA positive results for BND-35	Through study completion, up to approximately 34 months
Part 2: Progression Free Survival (PFS)	PFS is the time from the date of first dose of study drug to the date of first documented disease progression or death due to any cause, whichever occurs first.	Through study completion, up to approximately 24 months
Part 2: PFS rate	Percentage of participants with PFS, per RECIST v1.1	At 3, 6, 9, and 12 months, and up to 24 months
Part 2: Duration of Response	Duration between first documentation of CR or PR to first documentation of disease progression or death due to any cause, whichever occurs first	Through study completion, up to approximately 24 months
Part 2: Maximum observed plasma concentration (Cmax)	Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.	Through study completion, up to approximately 24 months
Part 2: Serum concentration at the end of the dosing interval (Ctrough)	Ctrough is the lowest concentration of drug reached before the next dose was administered.	Through study completion, up to approximately 24 months
Part 2: Time of maximum observed serum concentration (Tmax)	Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.	Through study completion, up to approximately 24 months
Part 2: Terminal elimination half-life (T1/2)	Terminal half-life is the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination.	Through study completion, up to approximately 24 months
Part 2: Area under the plasma concentration-time curve (AUC)	AUC is the area under the concentration-time curve of drug	Through study completion, up to approximately 24 months
Part 2: Incidence of anti-drug antibodies (ADA)	Number of participants with ADA positive results for BND-35	Through study completion, up to approximately 24 months

Collaborators and Investigators

• Sponsor: Biond Biologics
• Investigators: Study Director: Natalia Ashtamker, Biond Bio

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: February 21, 2024
• First Posted (Estimated): February 23, 2024

Study Record Updates

• Last Update Posted (Estimated): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Cetuximab
• Other Study ID Numbers: BND-35-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No