A Phase 1/2, Open-Label, Dose-Escalation Study of ISB 1302 in Subjects With HER2-Positive Metastatic Breast Cancer

Ichnos Sciences SA5 sites in 1 country1 target enrollmentApril 8, 2020

ConditionsBreast Cancer

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Breast Cancer
Sponsor: Ichnos Sciences SA
Enrollment: 1
Locations: 5
Primary Endpoint: Anti-tumor Activity of ISB 1302 administered Q1W (Part 2)
Status: Terminated
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to determine the safety profile, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of single agent ISB1302 in subjects with HER2-positive metastatic breast cancer who have been treated with all known therapies known to confer clinical benefit.

Detailed Description

To determine the safety profile, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of single agent ISB 1302 in subjects with HER2-positive metastatic breast cancer who have been treated with all known therapies known to confer clinical benefit.

Registry

clinicaltrials.gov

Start Date

April 8, 2020

End Date

July 24, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Ichnos Sciences SA

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Females with HER2-positive \[IHC 2 +, with FISH confirmation\] or 3+ \[IHC or FISH\] metastatic breast cancer that has progressed on last therapy. No more than 4 lines of therapy in metastatic setting (of which no more than 2 lines should be anti-HER2 antibody-based therapy).
•Measurable disease, defined as per RECIST v1.
•Eastern Cooperative Oncology Group (ECOG ) performance-status score of 2 or less
•Adequate bone marrow, renal, and liver function.
•Recovered from any previous surgery and no history of major surgery within the last 28 days prior to start of study drug
•Must be willing to undergo pre-treatment and on-treatment biopsies in Part 1 and Part 2.

Exclusion Criteria

•Any suspected or proven immunocompromised state, or infections, such as history of positive human immunodeficiency virus (HIV), known active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV).
•Any history or evidence of clinically significant cardiovascular disease.
•Evidence of clinically significant cardiovascular and respiratory conditions
•Previous antineoplastic treatment with immune checkpoint regulator or comparable immunotherapy within 8 weeks of starting study drug.
•Chemotherapy, radiotherapy, molecular-targeted therapy, or biological therapies (including HER2-directed therapies) within 4 weeks of starting study drug
•Hormone therapy within 2 weeks of starting study medications.
•Diagnosed with another malignancy that requires active therapy
•Brain metastases that require directed therapy.
•Has not recovered from any therapy related toxicities from previous treatments.
•Use of any investigational drug within 4 weeks from the start of study drug.

Outcomes

Primary Outcomes

Anti-tumor Activity of ISB 1302 administered Q1W (Part 2)

Time Frame: Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months

Tumor Response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) (Part 2)

MTD: Number of DLTs (dose limiting toxicities) during the first 28 days after the first administrations of study drug (i.e. Cycle 1) in each cohort.

Time Frame: 28 days

MTD: Number of DLTs (dose limiting toxicities) during the first 28 days after the first administrations of study drug (i.e. Cycle 1) in each cohort.

RP2D: Incidence and severity of AEs, AESI, and SAEs, including but not limited to laboratory values, PK and biomarkers.

Secondary Outcomes

Additional preliminary anti-tumor clinical activity of ISB 1302 administered (Part 2)(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-2(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) -AUC0-tau(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IFN-γ(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- TNF-α(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Incidence, nature, and intensity of AEs according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Antitumor activity of ISB 1302 administered Q1W (Part 1)(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) - AUC0-t(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-6(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD3(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Immunogenicity of ISB 1302 administered Q1W (Part 1 and Part 2)(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers - CD127(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include Epigenetic evaluation of Tregs(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) -Cmax(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2)-tmax(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-10(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD25(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD69(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD4(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include tumor microenvironment markers(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include apoptotic markers(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Time to disease progression (Part 1 and Part 2)(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD8(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include T cells(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include Tumor Mutational Burden (TMB)(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include Epigenetic evaluation of T helper cells(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)
Exploratory: Duration of treatment (Part 1 and Part 2)(Treatment cycles of 28 days, treatment cycles may continue, if there is clinical benefit, until disease progression, unacceptable toxicity, withdrawal, or end of study or cycles may continue beyond disease progression, treatment cycles for up to 6 months)