Phase 1/2 Study of BDC-1001 as a Single Agent and in Combination with Nivolumab in Patients with Advanced HER2-Expressing Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bolt Biotherapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Dec 2023 → 15 Feb 2025

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bolt Biotherapeutics, Inc.

External identifiers

EU CT number

2024-518411-19-00

EudraCT number

2021-006812-10

ClinicalTrials.gov

NCT04278144

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Dose response, Pharmacokinetic, Efficacy, Therapy

Dose Escalation (Part 1 and Part 2):
*To define the safety and tolerability of BDC-1001 as monotherapy (Part 1) and in combination with nivolumab (Part 2) in patients with
advanced HER2-expressing solid tumors.
*To determine the RP2D for BDC-1001 as monotherapy (Part 1) and in combination with nivolumab (Part 2) in patients with advanced
HER2-expressing solid tumors.
Dose Expansion (Parts 3 and 4):
*To evaluate preliminary antitumor activity of BDC-1001 as monotherapy (Part 3) and in combination with nivolumab (Part 4) in
patients with advanced HER2+ solid tumors.

Secondary objectives 3

1. Part 1: To analyze pharmacokinetic (PK) characteristics of BDC-1001 in patients with advanced HER2-expressing solid tumors
2. To evaluate preliminary antitumor activity of BDC-1001 as monotherapy (Part 1) and in combination with nivolumab (Part 2) in patients with advanced HER2-expressing solid tumors
3. To evaluate the immunogenicity of BDC-1001 as monotherapy (Part 1) and in combination with nivolumab (Part 2) in patients with advanced HER2-expressing solid tumors

Conditions and MedDRA coding

Advanced HER2-Expressing Solid Tumors.

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

IPD plan description

Not applicable.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. For Part 1 and Part 2: a. Patient has an advanced solid tumor for which approved therapies have been exhausted or for which the Investigator considers the patient ineligible or intolerant of other forms of treatment b. Tumor has documented HER2 expression (including both HER2-low and HER2+). At least 1 of the first 3 patients evaluated for DLT in Cohort M2 and all subsequent cohorts in Part 1 requires documented HER2 protein expression (IHC2+ or IHC3+) in tumor tissue.
2. For Part 3 and Part 4: a. Patient has an advanced HER2-positive solid tumor (defined as IHC 3+ or HER2 gene amplification) for which approved therapies have been exhausted or for which the Investigator considers the patient ineligible or intolerant of other forms of treatment and also has some conditions.
3. Age greater than or equal to 18 years old
4. Mentally competent and able to understand and sign the informed consent form
5. Eastern Cooperative Oncology Group performance status of 0 or 1
6. Expected life expectancy of greater than 12 weeks per the Investigator
7. Has LVEF ≥ 50% by either echocardiography or multiple-gated acquisition within 28 days before C1D1
8. Has disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
9. Parts 1 and 2: Able to provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue block and consent to collection of screening tumor biopsy for exploratory biomarker evaluation. If an archival block is unavailable, at least 15 freshly sectioned unstained slides may be submitted. Parts 3 and 4: Pre-treatment tumor tissue biopsy should be conducted, and fresh tissue submitted. If a fresh biopsy is not safely accessible or clinically feasible, an archival tumor tissue specimen must be submitted.
10. Willing and able to provide blood samples prior to the start of this study
11. At least 4 weeks post-op from prior major surgery
12. Laboratory values at Screening must be according to protocol.
13. Women of childbearing potential 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 7 months after the end of treatment
14. Potent men who are partners of women of childbearing potential must be willing to use condoms in combination with a second highly effective method (as above) of female contraception during the study and until 7 months after the end of treatment. A male partner will be considered as potent unless surgically sterilized (with appropriate documentation of sterility).

Exclusion criteria 13

1. Exclusion Criteria (Section 4.2): 1. For Part 2 and Part 4 with BDC-1001 and nivolumab combination therapy: a. Patient has a history of immune-mediated colitis. b. Patient has an active autoimmune disease with the exception of auto-immune endocrinopathies that are stable on hormone replacement therapy. c. History of allergy or hypersensitivity to nivolumab components. d. History of life-threatening toxicity related to prior immune therapy (eg, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) or anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) (PD-1/ PD-L1) treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg, Hypothyroidism).
2. Cardiovascular exclusions: a. Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or a cardiac arrhythmia that requires treatment. b. Has a medical history of myocardial infarction or unstable angina within 6 months before C1D1. c. Has a mean QT corrected—Fridericia’s formula (QTcF) prolongation of > 450 milliseconds (ms) in males and > 470 ms in females based on a 12-lead electrocardiogram (ECG) in triplicate. d. Has a medical history of an arterial thrombotic event, stroke, or transient ischemia attack within the past 12 months.
3. Other exclusions according to protocol.
4. Patient has known human immunodeficiency virus (HIV) infection (by antibody test), active hepatitis B infection (by hepatitis B surface antigen [HbsAg] test), or hepatitis C infection (by antibody test followed by confirmatory RNA test if antibody test is positive).
5. Patient is unwilling to use highly-effective contraceptive methods (as per Inclusion Section 4.1).
6. Patient has untreated central nervous system or brain metastases except for disease that is asymptomatic, clinically stable, and has not required steroids for at least 14 days prior to C1D1.
7. Patient taking steroids exceeding 10 mg/day prednisone or equivalent dose. Inhaled, intranasal, intraocular, topical, and intraarticular joint injections of corticosteroids are allowed
8. Patient has a serious illness considered by the Investigator as incompatible with participating in the protocol.
9. Patient is unwilling or unable to follow protocol requirements.
10. Patient has had an organ transplantation.
11. Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to C1D1 (ie, participants with a history of prior malignancy are eligible if treatment was completed at least 2 years before C1D1 and the patient has no evidence of disease). Participants with history of prior early stage basal/squamous cell skin cancer or non-invasive or in situ cancers that have undergone definitive treatment at any time are also eligible.
12. Patient has an active, known, or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
13. Any condition that, in the opinion of the Investigator, would interfere with evaluation of BDC-1001 or interpretation of the patient’s safety or study results.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Incidence of AEs and SAEs graded according to NCI CTCAE v5.0
2. Incidence and nature of DLTs within a 3 + 3 design
3. The occurrence of DLTs

Secondary endpoints 3

1. Pharmacokinetic variables may include: • Cmax • Cmin • AUC0-t • AUC0-inf • CL • Vz • t½
2. ORR using RECIST v1.1 • DCR of confirmed CR, confirmed PR, or stable disease (SD) lasting 24 weeks (- 7 days) or more weeks following the initiation of BDC-1001 • DoR • PFS
3. Incidence of ADAs against BDC-1001

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bolt Biotherapeutics Inc.

Sponsor organisation

Bolt Biotherapeutics Inc.

Address

900 Chesapeake Drive

City

Redwood City

Postcode

94063-4727

Country

United States

Scientific contact point

Organisation

Bolt Biotherapeutics Inc.

Contact name

Dawn Colburn

Public contact point

Organisation

Bolt Biotherapeutics Inc.

Contact name

Kristi Balacy

Third parties 13

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications