Study of BND-22 Administered Alone and in Combination With Other Therapeutics in Participants With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
This is an open-label, multicenter, dose escalation and expansion study designed to evaluate the safety, tolerability, and preliminary anti-tumor activity of BND-22 administered alone and in combination with pembrolizumab 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 and will be comprised of two parts - an initial "3 + 3" dose escalation phase followed by a dose expansion phase.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BND-22 Dose Escalation (Sub-Part 1A) Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. BND-22 will be administered intravenously (IV), every 2 weeks (Q2W). |
Drug: BND-22
Monoclonal antibody administered intravenously
|
| Experimental: BND-22 in Combination with Pembrolizumab Dose Escalation (Sub-Part 1B) Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. BND-22 and pembrolizumab will be administered intravenously (IV), every 3 weeks (Q3W). |
Drug: BND-22
Monoclonal antibody administered intravenously
Drug: Pembrolizumab
Monoclonal antibody administered intravenously
|
| Experimental: BND-22 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-22 and cetuximab will be administered intravenously (IV), every 2 weeks (Q2W). |
Drug: BND-22
Monoclonal antibody administered intravenously
Drug: Cetuximab
Monoclonal antibody administered intravenously
|
| Experimental: BND-22 Dose Expansion (Part 2) Will include three expansion cohorts enrolling patients with advanced stage squamous cell carcinoma of the head and neck, gastric or gastroesophageal junction adenocarcinoma, and non-small cell lung cancer. Enrollment will start after the RP2D of BND-22 has been established. BND-22 will be administered intravenously (IV), every 2 weeks (Q2W). |
Drug: BND-22
Monoclonal antibody administered intravenously
|
Outcome Measures
Primary Outcome Measures
- Part 1: Incidence of treatment-emergent adverse events (TEAEs) dose limiting toxicities (DLT) [Cycle 1 (28 days)]
Incidence of TEAEs meeting protocol defined DLT criteria
- Part 1: Incidence of treatment-emergent adverse events [Through study completion, an average of 5 months]
- Part 2: Objective Response Rate (ORR) per RECIST v1.1 [Through study completion, an average of 3 months]
Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
Secondary Outcome Measures
- Part 1: Maximum observed plasma concentration [Cmax] [Through study completion, an average of 2 months]
- Part 2: Maximum observed plasma concentration [Cmax] [Through study completion, an average of 3 months]
- Part 1: Terminal elimination half-life [T1/2] [Through study completion, an average of 2 months]
- Part 2: Terminal elimination half-life [T1/2] [Through study completion, an average of 3 months]
- Part 1: Area under the plasma concentration-time curve [AUC] [Through study completion, an average of 2 months]
- Part 2: Area under the plasma concentration-time curve [AUC] [Through study completion, an average of 3 months]
- Part 1: Incidence of anti-drug antibodies (ADA) [Through study completion, an average of 5 months]
- Part 2: Incidence of anti-drug antibodies (ADA) [Through study completion, an average of 6 months]
- Part 2: Progression Free Survival [Through study completion, an average of 3 months]
Time from the date of first dose of study drug to the date of first documented disease progression or death
- Part 2: Duration of Response [Through study completion, an average of 6 months]
Duration between first documentation of CR or PR to first documentation of disease progression or death
- Part 2: Incidence of Serious Adverse Events and Adverse Events [Through study completion, an average of 6 months]
Eligibility Criteria
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 lab tests
-
Part 1: Following tumor types: Breast cancer, cervical cancer, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, hepatobiliary cancers (hepatocellular carcinoma (HCC), gallbladder cancer, cholangiocarcinoma), non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the skin, or urothelial carcinoma
-
Part 2: Following tumor types: Squamous cell carcinoma of the head and neck, Gastric or gastroesophageal junction adenocarcinoma, Non-small cell lung cancer
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
-
Non-HCC patients: acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV); HCC patients: untreated active HBV or dual infection with HBV/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-EGFR 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/Concomitant Therapy:
-
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 macrophage or natural killer (NK) cells activating therapies
-
Administration of a live attenuated vaccine within 28 days
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic | Phoenix | Arizona | United States | 85054 |
| 2 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010 |
| 3 | University of Colorado Cancer Center | Aurora | Colorado | United States | 80045 |
| 4 | Yale Cancer Center | New Haven | Connecticut | United States | 06510 |
| 5 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 6 | Rambam Health Care Campus | Haifa | Israel | 3109601 | |
| 7 | Hadassah University Medical Center | Jerusalem | Israel | 91120 | |
| 8 | Rabin Medical Center | Petah Tikva | Israel | 49100 | |
| 9 | Sheba Medical Center | Ramat Gan | Israel | 52621 | |
| 10 | Tel Aviv Sourasky Medical Center | Tel Aviv | Israel | 6423906 |
Sponsors and Collaborators
- Biond Biologics
Investigators
- Study Director: Itay Friedman, MD, Biond Biologics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BND-22-001