Cancer
Conditions
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.
Interventions
DRUGBND-35
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
DRUGNivolumab
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
DRUGCetuximab
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Sponsors
Biond Biologics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) | Through study completion, up to approximately 34 months | 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. |
| Part 1: Proportion of patients who discontinued study treatment due to TEAEs | Through study completion, up to approximately 34 months | Number of patients who discontinued study treatment due to TEAEs |
| Part 1: Incidence of TEAEs dose limiting toxicities (DLT) | Up to 21 days in Cycle 1 | Incidence of TEAEs meeting protocol defined DLT criteria |
| Part 2: Objective Response Rate (ORR) per RECIST v1.1 | Through study completion, up to approximately 24 months | Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 |
| Part 2: Incidence of TEAEs and SAEs | Through study completion, an average of 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Objective Response Rate (ORR) per RECIST v1.1 | Through study completion, up to approximately 34 months | Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 |
| Part 1: Maximum observed plasma concentration (Cmax) | Through study completion, up to approximately 34 months | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. |
| Part 1: Serum concentration at the end of the dosing interval (Ctrough) | Through study completion, up to approximately 34 months | Ctrough is the lowest concentration of drug reached before the next dose was administered. |
| Part 1: Time of maximum observed serum concentration (Tmax) | Through study completion, up to approximately 34 months | Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve. |
| Part 1: Terminal elimination half-life (T1/2) | Through study completion, up to approximately 34 months | Terminal half-life is the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. |
| Part 1: Area under the plasma concentration-time curve (AUC) | Through study completion, up to approximately 34 months | AUC is the area under the concentration-time curve of drug |
| Part 1: Incidence of anti-drug antibodies (ADA) | Through study completion, up to approximately 34 months | Number of participants with ADA positive results for BND-35 |
| Part 2: Progression Free Survival (PFS) | Through study completion, up to approximately 24 months | 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. |
| Part 2: PFS rate | At 3, 6, 9, and 12 months, and up to 24 months | Percentage of participants with PFS, per RECIST v1.1 |
| Part 2: Duration of Response | Through study completion, up to approximately 24 months | Duration between first documentation of CR or PR to first documentation of disease progression or death due to any cause, whichever occurs first |
| Part 2: Maximum observed plasma concentration (Cmax) | Through study completion, up to approximately 24 months | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. |
| Part 2: Serum concentration at the end of the dosing interval (Ctrough) | Through study completion, up to approximately 24 months | Ctrough is the lowest concentration of drug reached before the next dose was administered. |
| Part 2: Time of maximum observed serum concentration (Tmax) | Through study completion, up to approximately 24 months | Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve. |
| Part 2: Terminal elimination half-life (T1/2) | Through study completion, up to approximately 24 months | Terminal half-life is the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. |
| Part 2: Area under the plasma concentration-time curve (AUC) | Through study completion, up to approximately 24 months | AUC is the area under the concentration-time curve of drug |
| Part 2: Incidence of anti-drug antibodies (ADA) | Through study completion, up to approximately 24 months | Number of participants with ADA positive results for BND-35 |
Countries
Israel
Contacts
STUDY_DIRECTORNatalia Ashtamker
Biond Bio
Outcome results
None listed