Not provided
Not provided
Not provided
Not provided
Not provided
Study terminated due to strategic considerations
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Estimated Study Duration:
Dose Escalation (Part 1): Approximately 34 months. Dose Optimization/Expansion (Part 2): Approximately 24 months.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| 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). |
|
| 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) |
|
| 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). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BND-35 | Drug | Pharmaceutical form: Solution for infusion; Route of administration: Intravenous |
|
| 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. |
| 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Natalia Ashtamker | Biond Bio | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rambam Health Care Campus | Haifa | 3109601 | Israel | |||
| Hadassah University Medical Center |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000911 | Antibodies, Monoclonal |
| D000077594 | Nivolumab |
| D000068818 | Cetuximab |
| ID | Term |
|---|---|
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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) |
|
|
| Nivolumab | Drug | Pharmaceutical form: Solution for infusion; Route of administration: Intravenous |
|
|
| Cetuximab | Drug | Pharmaceutical form: Solution for infusion; Route of administration: Intravenous |
|
|
| Through study completion, an average of 24 months |
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 |
| Jerusalem |
| 91120 |
| Israel |
| Rabin Medical Center | Petah Tikva | 49100 | Israel |
| Sheba Medical Center | Ramat Gan | 52621 | Israel |
| Tel Aviv Sourasky Medical Center | Tel Aviv | 6423906 | Israel |
| D011506 |
| Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D061067 | Antibodies, Monoclonal, Humanized |