A First-in-human Study of Multiple Doses of BB-1701 in Subjects With Locally Advanced/Metastatic HER2 Expressing Solid Tumors

NCT04257110 | Completed Phase 1 FDA Drug

• 1 other identifier: BB-1701-101
• Study Type: interventional
• Target: 117
• Locations: 2 countries
• Sites: 12

Brief Summary

This is an open-label, first-in-human (FIH), phase 1 dose-escalation and cohort expansion study of BB-1701 in subjects with locally advanced/metastatic HER2 expressing solid tumors. The study consists of 2 parts: dose-escalation (Part 1) and cohort expansion (Part 2). Part 1 consists of dose escalation cohorts for determining the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Part 2 consists of expansion cohorts, including but not limited to breast cancer, gastric/gastroesophageal junction cancer, bladder cancer and colon cancer, for exploring 1 or more RP2Ds or schedules for expanding/deepening the information/knowledge about clinical safety, clinical pharmacokinetics and anti-tumor activity.

Conditions

Locally Advanced/Metastatic HER2 Positive Solid Tumors

Keywords

Maximum tolerated dose; Recommended Phase 2 dose; First-in-human

Outcome Measures

Primary Outcomes (3)

• Number of subjects with adverse events and serious adverse events

  To evaluate the safety and tolerability of BB-1701

  up to 2 years

• Number of subjects with dose limiting toxicity (DLT)

  Subjects are evaluated for all study drug related and treatment emergent toxicities based on the National Cancer Institute Common Toxicity Criteria for adverse events (NCI-CTCAE)

  Cycle 1. Duration of each cycle is 21 days.

• MTD

  MTD is defined as the highest dose level at which no more than 1 out of 6 subjects experiences a DLT during the first cycle.

  Cycle 1. Duration of each cycle is 21 days.

Secondary Outcomes (6)

• Area under the serum concentration time curve from time 0 extrapolated to infinity (AUC0-inf)

  Cycle 1 Day 1. Duration of each cycle is 21 days.

• Maximum observed plasma concentration (Cmax)

  Pre-dose and post-dose during Cycle 1 through Cycle 8. Duration of each cycle is 21 days.

• Incidence of anti-drug antibodies

  Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of Cycles 2, 3, 4, 6, and 8. Duration of each cycle is 21 days.

• Objective response

  Every 9 weeks within 6 months and approximately every 12 weeks thereafter (up to 2 years)

• Progression Free Survival

  Every 9 weeks within 6 months and approximately every 12 weeks thereafter (up to 2 years)

Study Arms (5)

Part 1: Dose-escalation

OTHER

Eight doses levels have been selected for evaluation in the Part 1 of the study. Dose escalation decisions will be determined based on toxicities observed during the first cycle ( 21 days or 28 days).

Drug: BB-1701

Part 2: Cohort 1

EXPERIMENTAL

Breast Cancer with HER2 overexpressing or positive

Drug: BB-1701

Part 2: Cohort 2

EXPERIMENTAL

Breast Cancer with HER2 low expressing

Drug: BB-1701

Part 2 Cohort 3

EXPERIMENTAL

Gastric Cancer or gastroesophageal junction cancer with HER2 overexpressing or positive

Drug: BB-1701

Part 2 Cohort 4

EXPERIMENTAL

Solid Tumors other than Breast Cancer and Gastric Cancer with HER2 overexpressing or positive

Drug: BB-1701

Interventions

BB-1701 DRUG

BB-1701 will be administered as an intravenous infusion, every 3 weeks or every 4 weeks or every 6 weeks.

Part 1: Dose-escalation; Part 2 Cohort 3; Part 2 Cohort 4; Part 2: Cohort 1; Part 2: Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent for the trial.
• Male or female subject ≥ 18 years.
• Patients must have a histologically or cytologically confirmed locally advanced unresectable or metastatic HER2 expressing solid tumor(s) for which no curative therapy is available or tolerable
• Patients with breast cancer who are estrogen receptor (ER) and/or progesterone receptor (PR) positive and in whom hormonal therapy is indicated (e.g., patients with positive ER and/or PR without rapidly progressive or extensive visceral metastases) must have received at least 1 prior line of hormonal therapy
• Patients must have at least one measurable lesion as defined per RECIST Version 1.1.
• Patients must have a brain MRI (breast cancer only for part 2 cohort expansion) for the status of brain metastasis within 28 days prior to the first dose. Those with asymptomatic or stable CNS metastases are eligible for participation. However, patients with symptomatic and untreated CNS metastases, or those requiring ongoing treatment for CNS metastases, including steroids (\>10 mg of prednisone or 4 mg of dexamethasone) and antiepileptic agents should not be enrolled in the study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥12 weeks.
• Subjects (women of childbearing potential and males with fertile female partner) must be willing to use currently accepted reliable contraception method throughout the treatment period and for at least seven months following the last dose of study drug.
• Patients (women of childbearing potential and males with fertile female partner) must be willing to use currently accepted reliable contraception method throughout the treatment period and for at least six months following the last dose of study drug. These measures include, but are not limited to, oral or implantable injections of hormonal contraceptives; intrauterine birth control ring or placement of IUS intrauterine device); or use of barrier methods such as condoms or septum and spermicide products. Postmenopausal women over 50 years of age must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential must have a negative pregnancy test ≤ 7 days prior to the first dose of investigational product.
• Washout period required from the end of prior treatment to the first administration of the study drug
• Be able to provide a fresh formalin-fixed, paraffin-embedded (FFPE) tumor tissue block, or 5-10 non-staining tumor slides (cohort 4 should be within 2 years) for evaluation or confirmation or exploratory diagnostic tests of HER2 status.

You may not qualify if:

• Is receiving cancer therapy (chemotherapy or other systemic anti-cancer therapies, immunotherapy, radiation therapy, or surgery) at the time of enrollment.
• Has not recovered from adverse events (e.g., not returned to baseline or grade 0\~1) due to a previously administered agent.
• Had major surgery within 4 weeks before dosing, or will not have fully recovered from surgery; or has surgery planned during the time the subject is expected to participate in the study or within 4 weeks after the last dose of study drug administration
• Use of any investigational anti-cancer drug within 28 days before the first investigational product administration.
• Has received prior cumulative doxorubicin dose \> 360 mg/m² or equivalent
• Has grade 2 or higher peripheral neuropathy, or had a history of grade 3 or higher peripheral neuropathy or had a history of treatment discontinuation due to peripheral neuropathy
• Has an active pneumonitis/interstitial lung disease (ILD), a history of pneumonitis/ILD that required systemic steroids, received radiotherapy to lung field within 12 months before the first dose of study intervention, or current clinically relevant lung disease (e.g. Chronic Obstructive Pulmonary Disease).
• Has symptomatic or untreated CNS metastases, or those requiring ongoing treatment for CNS metastases, including steroids (\>10 mg of prednisone or 4 mg of dexamethasone) and antiepileptic agents.
• Any other serious underlying medical conditions, including but not limited to, uncontrolled diabetes mellitus, active uncontrolled infection, active gastric ulcer, uncontrolled seizures, cerebrovascular incidents, gastrointestinal bleeding, severe signs and symptoms of coagulation and clotting disorders
• Patients has clinically significant cardiovascular disease.
• QTc interval \>/= 450 msecs for male or \>/= 470 msecs for female \[Fridericia's formula: QTcF=QT msec/(RR sec)0.33).
• Current dyspnea at rest due to complications of advanced malignancy, or other diseases requiring continuous oxygen therapy.
• Any other serious underlying medical conditions, including but not limited to, psychiatric, psychological, familial or geographical condition that, in the judgment of the investigator, may interfere with the planned staging, treatment and follow-up, affect subject compliance or place the subject at high risk from treatment-related complications.
• History of seropositive status for human immunodeficiency virus (HIV) at any time before the start of treatment as determined by presence of anti-HIV-1 or anti-HIV-2 antibodies. Testing for seropositive status during Screening will be at the discretion of the investigator in participants without previously reported results.
• Active hepatitis B, or hepatitis C infection. Participants will be tested for hepatitis C virus (HCV) and hepatitis B virus (HBV) at screening:

Sponsors & Collaborators

• Bliss Biopharmaceutical (Hangzhou) Co., Ltd: lead

Study Sites (12)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

Sarah Cannon Research

Nashville, Tennessee, 37203, United States

Location

The Regents of NEXT Virginia, LLC

Fairfax, Virginia, 22031, United States

Location

Jiangsu Province Hospital

Nanjin, Jiangsu, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Location

Cancer Hospital Chinese Academy of Medical Science

Beijing, 100021, China

Location

Sun Yat-sen Memorial Hospital

Guangzhou, China

Location

The First Affiliated Hospital of Zhejiang University

Hangzhou, 310003, China

Location

Sir Run Run Shaw Hospital - Zhejiang University School of Medicine

Hangzhou, China

Location

Zhejiang Cancer Hospital

Hanzhou, China

Location

Linyi Cancer Hospital

Linyi, China

Location

Hubei Cancer Hospital

Wuhan, China

Location

Related Publications (1)

• Wang Y, Xia B, Cao L, Yang J, Feng C, Jiang F, Li C, Gu L, Yang Y, Tian J, Cheng X, Furuuchi K, Fulmer J, Verdi A, Rybinski K, Soto A, Albone E, Uenaka T, Gong L, Liu T, Qin Q, Wei Z, Zhou Y. Preclinical studies of BB-1701, a HER2-targeting eribulin-containing ADC with potent bystander effect and ICD activity. Antib Ther. 2024 Jun 25;7(3):221-232. doi: 10.1093/abt/tbae019. eCollection 2024 Jul.

  PMID: 39036069 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: February 5, 2020
• Study Start: July 28, 2020
• Primary Completion: August 31, 2024
• Study Completion: December 31, 2024
• Last Updated: July 24, 2025

Record last verified: 2025-07

Locations

CN (9); US (3)