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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06274437
• Other study ID #: BND-35-001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: April 2024
• Est. completion date: November 2027

Study information

• Verified date: February 2024
• Source: Biond Biologics
• Contact: Natalia Ashtamker, MD
• Phone: +972548886441
• Email: natalia[@]biondbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Estimated Study Duration:

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

Approximately 24 months.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 280
• Est. completion date: November 2027
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• BND-35
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
• Nivolumab
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
• Cetuximab
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Locations

Country	Name	City	State
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah University Medical Center	Jerusalem
Israel	Rabin Medical Center	Petah Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv

Sponsors (1)

Lead Sponsor	Collaborator
Biond Biologics

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Part 1: Incidence of TEAEs dose limiting toxicities (DLT)	Incidence of TEAEs meeting protocol defined DLT criteria	Up to 21 days in Cycle 1
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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