Clinical trial NCT03983395: Study of ISB 1302 (CD3 Bispecific Ab) in HER2-positive Metastatic Breast Cancer
Official title: A Phase 1/2, Open-Label, Dose-Escalation Study of ISB 1302 in Subjects With HER2-Positive Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: Breast Cancer
GBR 1302
HER2
HER2 x CD3 bispecific antibody
ISB 1302 (CD3 Bispecific Ab) in HER2-positive Metastatic Breast Cancer
Lead sponsor: Ichnos Sciences SA
Sponsor class: INDUSTRY
Collaborators: name: Glenmark Pharmaceuticals S.A.
First posted: 2019-06-12
Enrollment: 1
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 v1.1.
* 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.
* Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study drug or interpretation of subject safety or study results.

Primary outcomes:
measure: 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.
timeFrame: 28 days
measure: RP2D: Incidence and severity of AEs, AESI, and SAEs, including but not limited to laboratory values, PK and biomarkers.
timeFrame: 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
measure: Anti-tumor Activity of ISB 1302 administered Q1W (Part 2)
timeFrame: 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
Secondary outcomes:
measure: Incidence, nature, and intensity of AEs according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
timeFrame: 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
measure: Antitumor activity of ISB 1302 administered Q1W (Part 1)
timeFrame: 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
measure: Additional preliminary anti-tumor clinical activity of ISB 1302 administered (Part 2)
timeFrame: 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
measure: Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) -Cmax
timeFrame: 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
measure: Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2)-tmax
timeFrame: 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
measure: Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) -AUC0-tau
timeFrame: 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
measure: Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) - AUC0-t
timeFrame: 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
measure: Immunogenicity of ISB 1302 administered Q1W (Part 1 and Part 2)
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-2
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-6
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-10
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IFN-γ
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- TNF-α
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD3
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD4
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD8
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD25
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD69
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers - CD127
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include T cells
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include tumor microenvironment markers
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include apoptotic markers
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include Tumor Mutational Burden (TMB)
timeFrame: 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
measure: Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include Epigenetic evaluation of Tregs
timeFrame: 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
measure: 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
timeFrame: 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
measure: Exploratory: Duration of treatment (Part 1 and Part 2)
timeFrame: 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
measure: Exploratory: Time to disease progression (Part 1 and Part 2)
timeFrame: 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
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Ichnos Investigational Site 1
state: Arizona
city: Los Angeles
country: United States
facility: Ichnos Investigational Site 5
state: California
city: Louisville
country: United States
facility: Ichnos Investigational Site 4
state: Kentucky
city: Detroit
country: United States
facility: Ichnos Investigational Site 2
state: Michigan
city: Philadelphia
country: United States
facility: Ichnos Investigational Site 3
state: Pennsylvania
Study officials:
References: