Clinical Trials /

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

NCT04257110

Description:

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 positive 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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A First-in-human Study of Multiple Doses of BB-1701 in Subjects With Locally Advanced/Metastatic HER2 Positive Solid Tumors
  • Official Title: A First-in-human, Open Label, Multiple Dose, Dose Escalation and Cohort Expansion Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of BB-1701 in Subjects With Locally Advanced/Metastatic HER2 Positive Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BB-1701-101
  • NCT ID: NCT04257110

Conditions

  • Locally Advanced/Metastatic HER2 Positive Solid Tumors

Interventions

DrugSynonymsArms
BB-1701Part 1: Dose-escalation

Purpose

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 positive 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.

Detailed Description

      This is an open-label, FIH, phase 1 dose-escalation and cohort expansion study of BB-1701 in
      subjects with locally advanced /metastatic HER2 positive solid tumors. The study consists of
      2 parts: dose-escalation (Part 1) and cohort expansion (Part 2).

      Part 1 of this study will follow accelerated titration and traditional "3 + 3" design. Part 2
      is a cohort expansion study with HER2 positive locally advanced/metastatic solid tumors. Part
      2 consists of 2 cohorts: Cohort 1 includes subjects with HER2 positive breast cancer, who
      must have received prior 3 lines of HER2 targeting therapies and Cohort 2 includes subjects
      with HER2 positive cancers including but not limited to gastric/gastroesophageal junction
      cancer (GC/GEJ), bladder cancer and colon cancer; prior HER2 therapy not required for cancer
      types other than GC/GEJ.

      Study duration consists of Screening (up to 28 days), Treatment cycles (up to 8 cycles), and
      Safety Follow-up (30 days).
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose-escalationExperimentalEight 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.
  • BB-1701
Part 2: Cohort 1ExperimentalSubjects will be administered BB-1701 at one or two dose levels (e.g. MTD and the dose below MTD)
  • BB-1701
Part 2: Cohort 2ExperimentalSubjects will be administered BB-1701 at one or two dose levels (e.g. MTD and the dose below MTD)
  • BB-1701

Eligibility Criteria

        Inclusion Criteria:

          1. Willing and able to provide written informed consent for the trial.

          2. Male or female subject ≥ 18 years.

          3. Subjects must have a histologically or cytologically confirmed locally advanced
             unresectable or metastatic HER2 positive solid tumor(s) for which no curative therapy
             is available or tolerable.

          4. Subjects must have at least one measurable lesion as defined per RECIST Version 1.1.

          5. Eastern Cooperative Oncology Group performance status of 0 or 1.

          6. Life expectancy ≥12 weeks.

          7. Serum bilirubin ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase and
             alanine aminotransferase ≤ 2.0 × ULN OR ≤ 3.0 × ULN for subjects with liver
             metastases.

          8. 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.

        Exclusion Criteria:

          1. Subjects receiving cancer therapy at the time of enrollment.

          2. Has not recovered from adverse events due to a previously administered agent.

          3. Had major surgery within 4 weeks before dosing.

          4. Use of any investigational anti-cancer drug within 28 days before the first
             investigational product administration.

          5. Subjects who have received prior cumulative doxorubicin dose > 360 mg/m² or equivalent

          6. Subjects with > Grade 2 peripheral neuropathy

          7. 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

          8. Subjects with symptomatic or untreated central nervous system metastases, or those
             requiring ongoing treatment for central nervous system metastases, including steroids
             and antiepileptic agents.

          9. 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.

         10. Subjects with clinically significant cardiovascular disease, current dyspnea at rest
             due to complications of advanced malignancy.

         11. Active viral hepatitis (B or C)

         12. History of life-threatening hypersensitivity, or known to be allergic to protein drugs
             or recombinant proteins

         13. 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

         14. Females who are pregnant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with adverse events and serious adverse events
Time Frame:up to 2 years
Safety Issue:
Description:To evaluate the safety and tolerability of BB-1701

Secondary Outcome Measures

Measure:Area under the serum concentration time curve from time 0 extrapolated to infinity (AUC0-inf)
Time Frame:Cycle 1 Day 1. Duration of each cycle is 21 days.
Safety Issue:
Description:To characterize the pharmacokinetics (PK) of BB-1701
Measure:Maximum observed plasma concentration (Cmax)
Time Frame:Pre-dose and post-dose during Cycle 1 through Cycle 8. Duration of each cycle is 21 days.
Safety Issue:
Description:To characterize the PK of BB-1701
Measure:Incidence of anti-drug antibodies
Time Frame: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.
Safety Issue:
Description:To assess the immunogenicity of BB-1701
Measure:Objective response
Time Frame:Every 9 weeks within 6 months and approximately every 12 weeks thereafter (up to 2 years)
Safety Issue:
Description:To assess the preliminary anti-tumor activity of BB-1701
Measure:Progression Free Survival
Time Frame:Every 9 weeks within 6 months and approximately every 12 weeks thereafter (up to 2 years)
Safety Issue:
Description:To assess the preliminary anti-tumor activity of BB-1701
Measure:Duration of Response
Time Frame:Every 9 weeks within 6 months and approximately every 12 weeks thereafter (up to 2 years)
Safety Issue:
Description:To assess the preliminary anti-tumor activity of BB-1701

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bliss Biopharmaceutical (Hangzhou) Co., Ltd

Trial Keywords

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

Last Updated

March 3, 2020