Phase 2 Study of BB-1701 in HER2 positive or HER2-low metastatic breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eisai Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Aug 2024 → 18 Mar 2026

Decision date (initial)

2024-07-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-506866-30-00

WHO UTN

U1111-1305-1876

ClinicalTrials.gov

NCT06188559

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacokinetic, Safety, Efficacy

Dose Optimization (Part 1):
To determine the recommended dose (RD) of BB-1701 for Dose Expansion.
To assess the safety and tolerability of BB-1701 in each dose cohort.
Dose Expansion (Part 2):
To assess the antitumor activity of BB-1701 at the RD in the selected population(s) of breast cancer (BC) (based on observations from Part 1).

Secondary objectives 4

1. Dose Optimization (Part 1): To assess additional efficacy measures of BB-1701 in each dose cohort.
2. Dose Optimization (Part 1): To characterize the pharmacokinetics (PK) of BB-1701 and the relationship between BB-1701 exposure and selected efficacy and safety measures.
3. Dose Expansion (Part 2): To assess additional efficacy measures of BB-1701 at RD in the selected population(s) of BC.
4. Dose Expansion (Part 2): To assess the safety and tolerability of BB-1701 at RD.

Conditions and MedDRA coding

HER2 positive or HER2-low metastatic breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Subject must be willing and able to comply with all aspects of the protocol and as such provide written informed consent prior to any study-specific screening procedures.
2. Male or female, aged ≥18 years at the time of informed consent.
3. Metastatic or unresectable BC that is histologically confirmed to be either HER2-positive (defined as an immunohistochemistry [IHC] status of 3+, or a positive in situ hybridization [ISH] test [fluorescence, chromogenic, or silver-enhanced ISH] if IHC status is 2+) or HER2- low (defined as an IHC status of 1+, or 2+ and negative ISH) per the American Society of Clinical Oncology/College of American Pathology guidelines as documented prior to T-DXd treatment.
4. Must have previously received T-DXd.
5. Sufficient tumor tissue is required for HER2 status testing at a central laboratory.
6. Measurable disease meeting the following criteria as assessed by the investigator:according to RECIST 1.1. NOTE: Subjects with bone only disease may be eligible if there is a measurable soft tissue component associated with the bone lesion.
7. Must have previously received at least 1 but no more than 3 prior chemotherapy-based regimens in the unresectable or metastatic setting. If recurrence occurred during or within 6 months of (neo)adjuvant chemotherapy, this would count as 1 line of chemotherapy.
8. If HR-positive HER2-low BC, must have previously received endocrine therapy and is not expected to further benefit from it.
9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
10. Life expectancy of at least 3 months.
11. Adequate organ function and laboratory parameters.

Exclusion criteria 12

1. Presence of brain or subdural metastases, unless subject has completed local therapy and has discontinued the use of corticosteroids for this indication for at least 2 weeks prior to starting treatment in this study.
2. Diagnosed with meningeal carcinomatosis.
3. Received anticancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, etc) or an investigational drug or device within the past 28 days or 5 half-lives, whichever is shorter.
4. Prior treatment with eribulin.
5. Any prior allergic reactions of Grade ≥3 to monoclonal antibodies or contraindication to the receipt of corticosteroids or any of the excipients (investigators should refer to the prescribing information for the selected corticosteroid).
6. Residual toxic effects of prior therapies or surgical procedures that is Grade ≥2 (except alopecia or anemia).
7. Grade ≥2 peripheral neuropathy or history of Grade ≥3 peripheral neuropathy or discontinued any prior treatment due to peripheral neuropathy.
8. Active pneumonitis/interstitial lung disease (ILD) or any clinically significant lung disease (eg, chronic obstructive pulmonary disease), history of Grade ≥2 pneumonitis/ILD, or received radiotherapy to lung fields within 12 months of Cycle 1 Day 1 of study treatment.
9. Any of the following cardiac conditions: - Congestive heart failure greater than New York Heart Association Class II or left ventricular ejection fraction (LVEF) <50% measured by multigated acquisition (MUGA) scan or echocardiogram. - Has a corrected QT interval prolongation per Fridericia formula (QTcF) >470 ms (for both males and females) based on screening triplicate 12-lead ECG.
10. Concomitant active infection requiring systemic treatment, except: - If known to be human immunodeficiency virus (HIV)-positive, must be on anti-HIV therapy for at least 4 weeks and have a CD4+ T-cell (CD4+) count ≥350 cells/μL and an HIV viral load less than 400 copies/mL - If meets the criteria for anti-hepatitis B virus (HBV) therapy, must agree to take anti-HBV therapy, if known to be HBV-positive as defined by positive hepatitis B surface antigen or hepatitis B core antibody. HBV viral load must be undetectable. - If known to be hepatitis C virus (HCV)-positive must have completed curative therapy for HCV. HCV viral load must be undetectable.
11. Known history of active bacillus tuberculosis (TB).
12. Any medical or other condition which, in the opinion of the investigator, would preclude the subject’s participation in the clinical study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part 1: Safety: adverse events (AEs), clinical laboratory tests, vital signs, body weight, 12-lead ECGs, ECOG PS.
2. Part 1: Objective response rate (ORR): defined as the proportion of subjects achieving a confirmed CR or confirmed PR by investigator assessment per RECIST 1.1.
3. Part 2: ORR by BICR assessment per RECIST 1.1.

Secondary endpoints 11

1. Part 1: Duration of response (DOR): defined as the time from the onset date of documented CR or PR for confirmed responses by investigator per RECIST 1.1 to the date of disease progression or death, whichever occurs first.
2. Part 1: PFS: defined as the time from the date of first dose to the date of the first documentation of disease progression by investigator per RECIST 1.1 or death, whichever occurs first
3. Part 1: Overall survival (OS): defined as the time from the date of first dose to the date of death
4. Part 1: Disease Control Rate (DCR): defined as the proportion of subjects with CR, PR, or stable disease (SD) (≥5 weeks from the first dose) by investigator per RECIST 1.1
5. Part 1: Clinical Benefit Rate (CBR): defined as the proportion of subjects with CR, PR, or durable SD (duration of SD ≥23 weeks) by investigator per RECIST 1.1.
6. Part 1: Time To Response (TTR): defined as the time from the date of first dose to the day of the first documented CR or PR for confirmed responses by investigator per RECIST 1.1
7. Part 1: Noncompartmental PK parameters for BB-1701, total antibody, and eribulin
8. Part 1: PK/pharmacodynamic relationships for selected efficacy and safety endpoints
9. Part 2: DOR, DCR, TTR, CBR, and PFS by BICR per RECIST 1.1
10. Part 2: OS
11. Part 2: AEs, clinical laboratory tests, vital signs, 12 lead ECG, and ECOG PS

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eisai Limited

Sponsor organisation

Eisai Limited

Address

European Knowledge Center, Mosquito Way Mosquito Way

City

Hatfield

Postcode

AL10 9SN

Country

United Kingdom

Scientific contact point

Organisation

Eisai Limited

Contact name

Medical Information

Public contact point

Organisation

Eisai Limited

Contact name

Medical Information

Third parties 21

Locations

3 EU/EEA countries · 19 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

Documents 27 files

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

Application history

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