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

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

A first-in-human study using BDC-3042 as a single agent and in combination with pembrolizumab in patients with advanced malignancies

Study Overview

• Status: Recruiting
• Conditions: Clear Cell Renal Cell Carcinoma; Head and Neck Cancer; Colorectal Cancer; Ovarian Cancer; Triple Negative Breast Cancer; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: BDC-3042; Drug: Pembrolizumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 167
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Bolt Biotherapeutics; Phone Number: +1 650 434 8640; Email: clinicaltrials@boltbio.com

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • NEXT Oncology
      • Principal Investigator: Andrae Vandross, MD
      • Contact: Briana Flores; Email: bflores@nextoncology.com
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Principal Investigator: Ecaterina Dumbrava, MD
      • Contact: Ping Fan; Phone Number: 713-837-6018; Email: pfan@mdanderson.org
      • Contact: Amber Kennon; Phone Number: 713-745-8661; Email: mkennon@mdanderson.org
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology
      • Contact: Briana Flores; Email: bflores@nextoncology.com
      • Principal Investigator: Sharon Wilks, MD
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia
      • Contact: Blake Patterson; Email: bpatterson@nextoncology.com
      • Principal Investigator: Mohamad Salkeni, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to understand and sign the informed consent form
2. Age 18 years or older at the time of informed consent
3. Has disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

5. 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.

6. 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.

7. Adequate organ function defined as follows:

   1. 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)
   2. Renal: creatinine clearance ≥ 30 mL/min by Cockcroft-Gault estimate
   3. Coagulation: Prothrombin time or international normalized ratio and activated partial thromboplastin time ≤ 1.5 × upper limit of normal (ULN) (unless receiving anticoagulation therapy)
   4. 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)
8. Developed tumor progression after treatment with all standard therapies or have no appropriate available therapies
9. Expected life expectancy of > 12 weeks per the Investigator
10. 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.
11. 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:

1. Active systemic yeast infection within 4 weeks before study treatment
2. Prior hospitalization for asthma during past year
3. 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

4. Cardiac disease including:

   1. Congestive heart failure New York Heart Association classes II-IV
   2. QTcF prolongation > 450 milliseconds (ms) based on a 12-lead electrocardiogram (ECG) in triplicate or > 480 ms for subjects with bundle branch block
   3. Serious or uncontrolled cardiac arrhythmia within 6 months before starting study treatment
   4. Myocardial infarction, unstable angina pectoris, or coronary angioplasty, stenting, or surgery within 6 months before starting study treatment
   5. Serious or uncontrolled hypertension (≥ 180 mmHg systolic or ≥ 120 mmHg diastolic) within 6 months before starting study treatment
   6. Pericarditis or pericardial effusion that is symptomatic within 6 months before starting study treatment
5. 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)
6. Hepatic disease resulting in symptomatic ascites, encephalopathy, coagulopathy, esophageal/gastric varices, or persistent jaundice
7. Arterial thrombotic event, stroke, or transient ischemia attack within 6 months before starting study treatment
8. Bleeding diathesis or uncontrolled bleeding within 7 days before starting study treatment
9. Bone marrow transplant or solid organ transplant

10. Infection including:

    1. Disease requiring systemic therapy within 7 days before starting study treatment
    2. Ongoing COVID-19 as determined by viral testing
    3. Active human immunodeficiency virus (HIV) infection as determined at screening
    4. Active hepatitis B infection as determined at screening
    5. Active hepatitis C infection as determined at screening
11. 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.)
12. History of hemophagocytic lymphohistiocytosis/macrophage activation syndrome
13. 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
14. 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

15. Residual toxicity from previous treatment including:

    1. Toxicity related to prior treatment not resolved to Grade 1
    2. 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)
16. Subjects receiving immune checkpoint inhibitor: Toxicity Grade 3 related to prior immunotherapy and leading to treatment discontinuation
17. Any investigational agent within 28 days before starting study treatment or within 5 estimated elimination half-lives, whichever is shorter
18. Radiation therapy within 14 days before starting study treatment
19. History of severe hypersensitivity to any ingredient of BDC-3042 or study treatment (as applicable for combination study treatment)
20. Received live/attenuated virus vaccine within 28 days before starting study treatment
21. Major surgery within 28 days of starting study treatment (consult with Medical Monitor)
22. Actively enrolled in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study
23. Patient is a lactating mother or pregnant as confirmed by pregnancy tests within 7 days prior to start of study treatment
24. Patient is unwilling or unable to follow protocol requirements
25. Ongoing bowel perforation or presence of bowel fistula or intra-abdominal abscess
26. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single agent BDC-3042; Escalating doses followed by expansion targeting advanced malignancies	Drug: BDC-3042; Dectin-2 agonist antibody
Experimental: Combination BDC-3042 plus pembrolizumab; Escalating doses followed by expansion targeting advanced malignancies	Drug: BDC-3042; Dectin-2 agonist antibody; Drug: Pembrolizumab; Drug which blocks checkpoint proteins from binding with their partner proteins, allowing T cells to kill cancer cells; Other Names: Keytruda; Immune checkpoint inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to CTCAE v5.0	Escalation period	2 years
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	Up to 21 days
Objective response rate (ORR) using RECIST 1.1	Expansion period	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) using RECIST 1.1	Escalation period	2 years
Duration of response (DOR)	Escalation and expansion periods	2 years
Progression Free Survival (PFS)	Escalation and expansion periods	2 years
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	2 years
Best overall response (CR, PR, SD, progressive disease)	Expansion period	2 years
Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to CTCAE v5.0	Expansion period	2 years
PK (Cmax) of BDC-3042	Escalation and expansion periods	2 years
PK (Cmin) of BDC-3042	Escalation and expansion periods	2 years
PK (AUC0-t) of BDC-3042	Escalation and expansion periods	2 years
PK (AUC0-inf) of BDC-3042	Escalation and expansion periods	2 years
PK (CL) of BDC-3042	Escalation and expansion periods	2 years
PK (Vc or Vss) of BDC-3042	Escalation and expansion periods	2 years
PK (Terminal t1/2) of BDC-3042	Escalation and expansion periods	2 years
Incidence of anti-BDC-3042 antibodies	Escalation and expansion periods	2 years

Collaborators and Investigators

• Sponsor: Bolt Biotherapeutics, Inc.
• Investigators: Study Director: Bolt Clinical Development, Bolt Biotherapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: September 13, 2023
• First Submitted That Met QC Criteria: September 19, 2023
• First Posted (Actual): September 25, 2023

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Kidney Neoplasms; Breast Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab; Immune Checkpoint Inhibitors
• Other Study ID Numbers: BBI-20233042

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No