A Phase 2 Trial of BDC-1001 as Single Agent and in Combination with Pertuzumab in Subjects with Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Previously Treated with Trastuzumab Deruxtecan

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

15 Apr 2024 → 25 Sep 2024

Decision date (initial)

2024-02-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bolt Biotherapeutics Inc.

External identifiers

EU CT number

2023-506038-65-00

ClinicalTrials.gov

NCT05954143

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To evaluate the preliminary anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab in subjects with previously treated HER2+ MBC

Secondary objectives 4

1. Efficacy: To evaluate the preliminary anti-tumor activity of BDC-1001 as a single agent and in combination with pertuzumab in subjects with previously treated HER2+ MBC.
2. Safety: To determine the safety and tolerability of BDC-1001 as a single agent and in combination with pertuzumab in subjects with previously treated HER2+ MBC
3. PK: To evaluate the exposure profile of BDC- 1001 as a single agent and in combination with pertuzumab in subjects with previously treated HER2+ MBC
4. ADA: To evaluate the immunogenicity of BDC-1001 as a single agent and in combination with pertuzumab in subjects with previously treated HER2+ MBC

Conditions and MedDRA coding

HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2–POSITIVE METASTATIC BREAST CANCER

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Be able to understand and sign the informed consent form.
2. Be age 18 years or older at the time of informed consent.
3. All subjects must agree to have a biopsy prior to enrollment. If, in the judgement of the Investigator, a biopsy is not safely accessible or clinically feasible an archival tumor tissue must be submitted in lieu of a freshly collected specimen.
4. Histologically confirmed adenocarcinoma of the breast that is HER2+ (per 2018 ASCO/CAP HER2 testing guidelines) by Clinical Laboratory Improvement Amendments (CLIA) certified laboratory assessment
5. Have received 2 or more prior lines of anti- human epidermal growth factor receptor 2 (HER2)-directed therapies, at least 1 of them is in the metastatic setting and 1 of the prior therapies needs to be trastuzumab deruxtecan (ENHERTU®). Prior neo-adjuvant or adjuvant therapy that resulted in relapse within 12 months of completion of therapy will be considered a line of treatment for metastatic disease
6. Have experienced disease progression on or been otherwise unsuitable for (eg, did not tolerate) the most recent therapy
7. Have measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria
8. Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
9. Have expected life expectancy of greater than 12 weeks per the Investigator
10. Adequate organ function defined as per protocol.
11. Women of childbearing potential should agree not to donate eggs and must 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 treatment. Highly effective, alternative non-hormonal contraceptive measures are preferred.
12. Potent men that are partners of women of childbearing potential must be willing to use condoms in combination with a second highly effective method of female contraception (as above) during the study and agree not to donate sperm from Screening through 7 months after completion of study. A male partner will be considered as potent unless surgically sterilized (with documentation of sterility).

Exclusion criteria 22

1. Central nervous system metastases with the exception of disease that is asymptomatic, clinically stable (without evidence of progression for at least 4 weeks by repeating imaging during study Screening), and has not required steroids for at least 28 days before starting study treatment.
2. Cardiac disease as described in the protocol.
3. Pulmonary disease including idiopathic pulmonary fibrosis, interstitial lung disease, pneumonitis requiring steroids, or symptomatic pleural effusion within 6 months before starting study treatment OR ongoing requirement for supplemental oxygen
4. Hepatic disease resulting in symptomatic ascites, encephalopathy, coagulopathy, esophageal/gastric varices, or persistent jaundice
5. Arterial thrombotic event, stroke, or transient ischemia attack within 6 months before starting study treatment
6. Bleeding diathesis or uncontrolled bleeding within 7 days before starting study treatment
7. Bone marrow transplant or solid organ transplant
8. Infection included in the protocol.
9. 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.)
10. 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
11. Any medical condition requiring corticosteroids (> 10 mg daily oral prednisone or equivalent) or other systemic immunosuppressive therapy within 28 days before starting study treatment. Exceptions include inhaled or topical steroids
12. Residual toxicity from previous treatment as described in the protocol
13. Prior anticancer therapies as described in protocol.
14. History of severe hypersensitivity to any ingredient of BDC-1001 or pertuzumab
15. Received live/attenuated virus vaccine within 28 days before starting study treatment
16. Major surgery within 28 days of starting study treatment
17. Radiation therapy within 2 weeks of C1D1
18. Actively enrolled in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study
19. Subject is a lactating mother or pregnant as confirmed by pregnancy tests within 7 days prior to start of study treatment
20. Subject is unwilling or unable to follow protocol requirements.
21. Uncontrolled pleural effusion, pericardial effusion, or recurrent ascites drainage.
22. Any condition that, in the opinion of the Investigator, would interfere with evaluation of BDC-1001 and pertuzumab or interpretation of the subject’s safety or study results

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate according to RECIST v1.1

Secondary endpoints 5

1. Duration of response, disease control rate, progression free survival, overall survival
2. Incidence of treatment-emergent AEs and SAEs graded according to NCI CTCAE v5.0
3. Changes from baseline in vital signs, laboratory values, and ECGs
4. Cmin and Cmax values will be obtained throughout the study and compared to the PK data from the Phase 1 single agent BDC-1001 study utilizing a population approach
5. Incidence of anti-drug antibodies

Investigational products

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

Test 2

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

Trial Information Support

Public contact point

Organisation

Bolt Biotherapeutics Inc.

Contact name

Trial Information Support

Third parties 10

Locations

3 EU/EEA countries · 17 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 2 files

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

Application history

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