Clinical trial NCT06274437: A Study of BND-35 in Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cancer
Lead sponsor: Biond Biologics
Sponsor class: INDUSTRY
First posted: 2024-02-23
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Detailed description: Estimated Study Duration:

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

Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
timeFrame: Through study completion, up to approximately 34 months
measure: Part 1: Proportion of patients who discontinued study treatment due to TEAEs
timeFrame: Through study completion, up to approximately 34 months
measure: Part 1: Incidence of TEAEs dose limiting toxicities (DLT)
timeFrame: Up to 21 days in Cycle 1
measure: Part 2: Objective Response Rate (ORR) per RECIST v1.1
timeFrame: Through study completion, up to approximately 24 months
measure: Part 2: Incidence of TEAEs and SAEs
timeFrame: Through study completion, an average of 24 months
Secondary outcomes:
measure: Part 1: Objective Response Rate (ORR) per RECIST v1.1
timeFrame: Through study completion, up to approximately 34 months
measure: Part 1: Maximum observed plasma concentration (Cmax)
timeFrame: Through study completion, up to approximately 34 months
measure: Part 1: Serum concentration at the end of the dosing interval (Ctrough)
timeFrame: Through study completion, up to approximately 34 months
measure: Part 1: Time of maximum observed serum concentration (Tmax)
timeFrame: Through study completion, up to approximately 34 months
measure: Part 1: Terminal elimination half-life (T1/2)
timeFrame: Through study completion, up to approximately 34 months
measure: Part 1: Area under the plasma concentration-time curve (AUC)
timeFrame: Through study completion, up to approximately 34 months
measure: Part 1: Incidence of anti-drug antibodies (ADA)
timeFrame: Through study completion, up to approximately 34 months
measure: Part 2: Progression Free Survival (PFS)
timeFrame: Through study completion, up to approximately 24 months
measure: Part 2: PFS rate
timeFrame: At 3, 6, 9, and 12 months, and up to 24 months
measure: Part 2: Duration of Response
timeFrame: Through study completion, up to approximately 24 months
measure: Part 2: Maximum observed plasma concentration (Cmax)
timeFrame: Through study completion, up to approximately 24 months
measure: Part 2: Serum concentration at the end of the dosing interval (Ctrough)
timeFrame: Through study completion, up to approximately 24 months
measure: Part 2: Time of maximum observed serum concentration (Tmax)
timeFrame: Through study completion, up to approximately 24 months
measure: Part 2: Terminal elimination half-life (T1/2)
timeFrame: Through study completion, up to approximately 24 months
measure: Part 2: Area under the plasma concentration-time curve (AUC)
timeFrame: Through study completion, up to approximately 24 months
measure: Part 2: Incidence of anti-drug antibodies (ADA)
timeFrame: Through study completion, up to approximately 24 months
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah University Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
Study officials:
affiliation: Biond Bio
name: Natalia Ashtamker
role: STUDY_DIRECTOR
References: