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Study of BDC-3042 as Single Agent and in Combination With Pembrolizumab in Patients With Advanced Malignancies

Primary Purpose

Triple Negative Breast Cancer, Clear Cell Renal Cell Carcinoma, Ovarian Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BDC-3042
Pembrolizumab
Sponsored by
Bolt Biotherapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Able to understand and sign the informed consent form Age 18 years or older at the time of informed consent Has disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Subjects enrolled in Part 1 and Part 2 dose escalation cohorts must have: a. Histologically/cytologically confirmed triple-negative breast cancer (TNBC), clear cell renal cell cancer (ccRCC), ovarian cancer, head and neck cancer, colorectal cancer, or non-small cell lung cancer (NSCLC) that is metastatic or unresectable with tumor progression after standard therapy who have no options for standard therapies which are known to confer clinical benefit. Subjects with ovarian cancer must have platinum resistant or platinum-refractory tumors. Subjects enrolled in Part 3 and Part 4 dose expansion cohorts must have histologically/cytologically confirmed metastatic or unresectable TNBC or NSCLC with tumor progression after standard therapy who have no options for standard therapies which are known to confer clinical benefit. Adequate organ function defined as follows: Hematology: i. Absolute neutrophil count ≥ 1500 cells/mm3; ii. Platelet count ≥ 75,000 cells/mm3; iii. Hemoglobin ≥ 9 g/dL (and without transfusion within 7 days) Renal: creatinine clearance ≥ 30 mL/min by Cockcroft-Gault estimate Coagulation: Prothrombin time or international normalized ratio and activated partial thromboplastin time ≤ 1.5 × upper limit of normal (ULN) (unless receiving anticoagulation therapy) Hepatic: i. Aspartate aminotransferase and alanine transaminase (ALT) ≤ 3 × ULN (or ≤ 5 × ULN in subjects with known hepatic metastases); ii. Total bilirubin ≤ 1.5 × ULN (isolated value > 1.5 × ULN is acceptable if direct bilirubin is < 35% of total) Developed tumor progression after treatment with all standard therapies or have no appropriate available therapies Expected life expectancy of > 12 weeks per the Investigator Women of childbearing potential (WOCBP) should use a highly effective contraceptive measure (a method that can achieve a failure rate of less than 1% per year) during treatment and until 4 weeks after the end treatment. Potent men that are partners of WOCBP must be willing to use condoms in combination with a second highly effective method of female contraception and agree not to donate sperm from screen through at least 4 months after last dose of study treatment. A male partner will be considered as potent unless surgically sterilized (with appropriate documentation of sterility). Exclusion Criteria: Active systemic yeast infection within 4 weeks before study treatment Prior hospitalization for asthma during past year Central nervous system metastases except for disease that is asymptomatic, clinically stable, and has not required steroids for at least 14 days before starting study treatment Cardiac disease including: Congestive heart failure New York Heart Association classes II-IV QTcF prolongation > 450 milliseconds (ms) based on a 12-lead electrocardiogram (ECG) in triplicate or > 480 ms for subjects with bundle branch block Serious or uncontrolled cardiac arrhythmia within 6 months before starting study treatment Myocardial infarction, unstable angina pectoris, or coronary angioplasty, stenting, or surgery within 6 months before starting study treatment Serious or uncontrolled hypertension (≥ 180 mmHg systolic or ≥ 120 mmHg diastolic) within 6 months before starting study treatment Pericarditis or pericardial effusion that is symptomatic within 6 months before starting study treatment Pulmonary disease including idiopathic pulmonary fibrosis, noninfectious interstitial lung disease, pneumonitis, chronic obstructive pulmonary disease (requiring daily treatment for dyspnea, oxygen therapy on an ongoing basis, or hospitalization within the past 6 months) Hepatic disease resulting in symptomatic ascites, encephalopathy, coagulopathy, esophageal/gastric varices, or persistent jaundice Arterial thrombotic event, stroke, or transient ischemia attack within 6 months before starting study treatment Bleeding diathesis or uncontrolled bleeding within 7 days before starting study treatment Bone marrow transplant or solid organ transplant Infection including: Disease requiring systemic therapy within 7 days before starting study treatment Ongoing COVID-19 as determined by viral testing Active human immunodeficiency virus (HIV) infection as determined at screening Active hepatitis B infection as determined at screening Active hepatitis C infection as determined at screening Autoimmune disease requiring systemic disease-modifying or immunosuppressive therapy within 2 years before starting study treatment. Exceptions include disease managed with only replacement therapies (eg, thyroxine, etc.) History of hemophagocytic lymphohistiocytosis/macrophage activation syndrome Malignancy within 2 years before starting study treatment other than the disease under study. Exceptions include indolent or definitively treated disease not expected to require treatment during the study, affect the safety of subjects, or affect the endpoints of the trial Any medical condition requiring corticosteroids (> 10 mg daily oral prednisone or equivalent) or other systemic immunosuppressive therapy within 28 days before starting study treatment. Exception: Intermittent or sporadic use of inhaled or topical steroids is allowed Residual toxicity from previous treatment including: Toxicity related to prior treatment not resolved to Grade 1 Neuropathy Grade > 2 Note: Exceptions to the above criteria include toxicities that do not pose a risk to vital organ systems (eg, alopecia) or toxicities that are stable as managed by replacement therapies (eg, hypothyroidism) Subjects receiving immune checkpoint inhibitor: Toxicity Grade 3 related to prior immunotherapy and leading to treatment discontinuation Any investigational agent within 28 days before starting study treatment or within 5 estimated elimination half-lives, whichever is shorter Radiation therapy within 14 days before starting study treatment History of severe hypersensitivity to any ingredient of BDC-3042 or study treatment (as applicable for combination study treatment) Received live/attenuated virus vaccine within 28 days before starting study treatment Major surgery within 28 days of starting study treatment (consult with Medical Monitor) Actively enrolled in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study Patient is a lactating mother or pregnant as confirmed by pregnancy tests within 7 days prior to start of study treatment Patient is unwilling or unable to follow protocol requirements Ongoing bowel perforation or presence of bowel fistula or intra-abdominal abscess Any condition that, in the opinion of the Investigator, would interfere with evaluation of BDC-3042 or interpretation of the patient's safety or study results

Sites / Locations

  • NEXT OncologyRecruiting
  • NEXT OncologyRecruiting
  • NEXT VirginiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Single agent BDC-3042

Combination BDC-3042 plus pembrolizumab

Arm Description

Escalating doses followed by expansion targeting advanced malignancies

Escalating doses followed by expansion targeting advanced malignancies

Outcomes

Primary Outcome Measures

Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to CTCAE v5.0
Escalation period
Incidence and nature of AEs considered by the Investigator or Sponsor to be clinically relevant, attributable to study treatment, and meeting dose-limiting toxicity (DLT) criteria
Escalation period
Objective response rate (ORR) using RECIST 1.1
Expansion period

Secondary Outcome Measures

Objective response rate (ORR) using RECIST 1.1
Escalation period
Duration of response (DOR)
Escalation and expansion periods
Disease control rate (DCR) of confirmed complete response (CR), partial response (PR), or stable disease (SD) lasting 4 or more weeks
Escalation and expansion periods
Progression Free Survival (PFS)
Escalation and expansion periods
Best overall response (CR, PR, SD, progressive disease)
Expansion period
Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to CTCAE v5.0
Expansion period
PK (Cmax) of BDC-3042
Escalation and expansion periods
PK (Cmin) of BDC-3042
Escalation and expansion periods
PK (AUC0-t) of BDC-3042
Escalation and expansion periods
PK (AUC0-inf) of BDC-3042
Escalation and expansion periods
PK (CL) of BDC-3042
Escalation and expansion periods
PK (Vc or Vss) of BDC-3042
Escalation and expansion periods
PK (Terminal t1/2) of BDC-3042
Escalation and expansion periods
Incidence of anti-BDC-3042 antibodies
Escalation and expansion periods

Full Information

First Posted
September 13, 2023
Last Updated
September 19, 2023
Sponsor
Bolt Biotherapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT06052852
Brief Title
Study of BDC-3042 as Single Agent and in Combination With Pembrolizumab in Patients With Advanced Malignancies
Official Title
A Phase 1/2, First-in-Human, Dose Escalation and Expansion Study of BDC-3042 as a Single Agent and in Combination With Pembrolizumab in Patients With Advanced Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
March 2026 (Anticipated)
Study Completion Date
March 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bolt Biotherapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A first-in-human study using BDC-3042 as a single agent and in combination with pembrolizumab in patients with advanced malignancies
Detailed Description
This study has four parts. Part 1 is a dose escalation of BDC-3042 as a single agent to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), or maximum protocol dose (MPD) recommended for Part 3. In Part 3, the selected dose will be administered as monotherapy to patients with selected advanced malignancies. Part 2 is a dose escalation of BDC-3042 in combination with pembrolizumab to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), or maximum protocol dose (MPD) recommended for Part 4. In Part 4, the selected dose will be administered in combination with pembrolizumab to patients with selected advanced malignancies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple Negative Breast Cancer, Clear Cell Renal Cell Carcinoma, Ovarian Cancer, Head and Neck Cancer, Colorectal Cancer, Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Multiple ascending dose and dose-expansion of BDC-3042 administered as a single agent or in combination with pembrolizumab
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
167 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single agent BDC-3042
Arm Type
Experimental
Arm Description
Escalating doses followed by expansion targeting advanced malignancies
Arm Title
Combination BDC-3042 plus pembrolizumab
Arm Type
Experimental
Arm Description
Escalating doses followed by expansion targeting advanced malignancies
Intervention Type
Drug
Intervention Name(s)
BDC-3042
Intervention Description
Dectin-2 agonist antibody
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, Immune checkpoint inhibitor
Intervention Description
Drug which blocks checkpoint proteins from binding with their partner proteins, allowing T cells to kill cancer cells
Primary Outcome Measure Information:
Title
Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to CTCAE v5.0
Description
Escalation period
Time Frame
2 years
Title
Incidence and nature of AEs considered by the Investigator or Sponsor to be clinically relevant, attributable to study treatment, and meeting dose-limiting toxicity (DLT) criteria
Description
Escalation period
Time Frame
Up to 21 days
Title
Objective response rate (ORR) using RECIST 1.1
Description
Expansion period
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Objective response rate (ORR) using RECIST 1.1
Description
Escalation period
Time Frame
2 years
Title
Duration of response (DOR)
Description
Escalation and expansion periods
Time Frame
2 years
Title
Disease control rate (DCR) of confirmed complete response (CR), partial response (PR), or stable disease (SD) lasting 4 or more weeks
Description
Escalation and expansion periods
Time Frame
2 years
Title
Progression Free Survival (PFS)
Description
Escalation and expansion periods
Time Frame
2 years
Title
Best overall response (CR, PR, SD, progressive disease)
Description
Expansion period
Time Frame
2 years
Title
Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to CTCAE v5.0
Description
Expansion period
Time Frame
2 years
Title
PK (Cmax) of BDC-3042
Description
Escalation and expansion periods
Time Frame
2 years
Title
PK (Cmin) of BDC-3042
Description
Escalation and expansion periods
Time Frame
2 years
Title
PK (AUC0-t) of BDC-3042
Description
Escalation and expansion periods
Time Frame
2 years
Title
PK (AUC0-inf) of BDC-3042
Description
Escalation and expansion periods
Time Frame
2 years
Title
PK (CL) of BDC-3042
Description
Escalation and expansion periods
Time Frame
2 years
Title
PK (Vc or Vss) of BDC-3042
Description
Escalation and expansion periods
Time Frame
2 years
Title
PK (Terminal t1/2) of BDC-3042
Description
Escalation and expansion periods
Time Frame
2 years
Title
Incidence of anti-BDC-3042 antibodies
Description
Escalation and expansion periods
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to understand and sign the informed consent form Age 18 years or older at the time of informed consent Has disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Subjects enrolled in Part 1 and Part 2 dose escalation cohorts must have: a. Histologically/cytologically confirmed triple-negative breast cancer (TNBC), clear cell renal cell cancer (ccRCC), ovarian cancer, head and neck cancer, colorectal cancer, or non-small cell lung cancer (NSCLC) that is metastatic or unresectable with tumor progression after standard therapy who have no options for standard therapies which are known to confer clinical benefit. Subjects with ovarian cancer must have platinum resistant or platinum-refractory tumors. Subjects enrolled in Part 3 and Part 4 dose expansion cohorts must have histologically/cytologically confirmed metastatic or unresectable TNBC or NSCLC with tumor progression after standard therapy who have no options for standard therapies which are known to confer clinical benefit. Adequate organ function defined as follows: Hematology: i. Absolute neutrophil count ≥ 1500 cells/mm3; ii. Platelet count ≥ 75,000 cells/mm3; iii. Hemoglobin ≥ 9 g/dL (and without transfusion within 7 days) Renal: creatinine clearance ≥ 30 mL/min by Cockcroft-Gault estimate Coagulation: Prothrombin time or international normalized ratio and activated partial thromboplastin time ≤ 1.5 × upper limit of normal (ULN) (unless receiving anticoagulation therapy) Hepatic: i. Aspartate aminotransferase and alanine transaminase (ALT) ≤ 3 × ULN (or ≤ 5 × ULN in subjects with known hepatic metastases); ii. Total bilirubin ≤ 1.5 × ULN (isolated value > 1.5 × ULN is acceptable if direct bilirubin is < 35% of total) Developed tumor progression after treatment with all standard therapies or have no appropriate available therapies Expected life expectancy of > 12 weeks per the Investigator Women of childbearing potential (WOCBP) should use a highly effective contraceptive measure (a method that can achieve a failure rate of less than 1% per year) during treatment and until 4 weeks after the end treatment. Potent men that are partners of WOCBP must be willing to use condoms in combination with a second highly effective method of female contraception and agree not to donate sperm from screen through at least 4 months after last dose of study treatment. A male partner will be considered as potent unless surgically sterilized (with appropriate documentation of sterility). Exclusion Criteria: Active systemic yeast infection within 4 weeks before study treatment Prior hospitalization for asthma during past year Central nervous system metastases except for disease that is asymptomatic, clinically stable, and has not required steroids for at least 14 days before starting study treatment Cardiac disease including: Congestive heart failure New York Heart Association classes II-IV QTcF prolongation > 450 milliseconds (ms) based on a 12-lead electrocardiogram (ECG) in triplicate or > 480 ms for subjects with bundle branch block Serious or uncontrolled cardiac arrhythmia within 6 months before starting study treatment Myocardial infarction, unstable angina pectoris, or coronary angioplasty, stenting, or surgery within 6 months before starting study treatment Serious or uncontrolled hypertension (≥ 180 mmHg systolic or ≥ 120 mmHg diastolic) within 6 months before starting study treatment Pericarditis or pericardial effusion that is symptomatic within 6 months before starting study treatment Pulmonary disease including idiopathic pulmonary fibrosis, noninfectious interstitial lung disease, pneumonitis, chronic obstructive pulmonary disease (requiring daily treatment for dyspnea, oxygen therapy on an ongoing basis, or hospitalization within the past 6 months) Hepatic disease resulting in symptomatic ascites, encephalopathy, coagulopathy, esophageal/gastric varices, or persistent jaundice Arterial thrombotic event, stroke, or transient ischemia attack within 6 months before starting study treatment Bleeding diathesis or uncontrolled bleeding within 7 days before starting study treatment Bone marrow transplant or solid organ transplant Infection including: Disease requiring systemic therapy within 7 days before starting study treatment Ongoing COVID-19 as determined by viral testing Active human immunodeficiency virus (HIV) infection as determined at screening Active hepatitis B infection as determined at screening Active hepatitis C infection as determined at screening Autoimmune disease requiring systemic disease-modifying or immunosuppressive therapy within 2 years before starting study treatment. Exceptions include disease managed with only replacement therapies (eg, thyroxine, etc.) History of hemophagocytic lymphohistiocytosis/macrophage activation syndrome Malignancy within 2 years before starting study treatment other than the disease under study. Exceptions include indolent or definitively treated disease not expected to require treatment during the study, affect the safety of subjects, or affect the endpoints of the trial Any medical condition requiring corticosteroids (> 10 mg daily oral prednisone or equivalent) or other systemic immunosuppressive therapy within 28 days before starting study treatment. Exception: Intermittent or sporadic use of inhaled or topical steroids is allowed Residual toxicity from previous treatment including: Toxicity related to prior treatment not resolved to Grade 1 Neuropathy Grade > 2 Note: Exceptions to the above criteria include toxicities that do not pose a risk to vital organ systems (eg, alopecia) or toxicities that are stable as managed by replacement therapies (eg, hypothyroidism) Subjects receiving immune checkpoint inhibitor: Toxicity Grade 3 related to prior immunotherapy and leading to treatment discontinuation Any investigational agent within 28 days before starting study treatment or within 5 estimated elimination half-lives, whichever is shorter Radiation therapy within 14 days before starting study treatment History of severe hypersensitivity to any ingredient of BDC-3042 or study treatment (as applicable for combination study treatment) Received live/attenuated virus vaccine within 28 days before starting study treatment Major surgery within 28 days of starting study treatment (consult with Medical Monitor) Actively enrolled in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study Patient is a lactating mother or pregnant as confirmed by pregnancy tests within 7 days prior to start of study treatment Patient is unwilling or unable to follow protocol requirements Ongoing bowel perforation or presence of bowel fistula or intra-abdominal abscess Any condition that, in the opinion of the Investigator, would interfere with evaluation of BDC-3042 or interpretation of the patient's safety or study results
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bolt Biotherapeutics
Phone
+1 650 434 8640
Email
clinicaltrials@boltbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bolt Clinical Development
Organizational Affiliation
Bolt Biotherapeutics
Official's Role
Study Director
Facility Information:
Facility Name
NEXT Oncology
City
Austin
State/Province
Texas
ZIP/Postal Code
78758
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Briana Flores
Email
bflores@nextoncology.com
Facility Name
NEXT Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Briana Flores
Email
bflores@nextoncology.com
Facility Name
NEXT Virginia
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Blake Patterson
Email
bpatterson@nextoncology.com

12. IPD Sharing Statement

Learn more about this trial

Study of BDC-3042 as Single Agent and in Combination With Pembrolizumab in Patients With Advanced Malignancies

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