Study of ISB 1302 (CD3 Bispecific Ab) in HER2-positive Metastatic Breast Cancer

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

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03983395

Enrollment

Registered

2019-06-12

Start date

2020-04-08

Completion date

2020-07-24

Last updated

2021-05-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

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.

Interventions

BIOLOGICALISB 1302 250 ng/kg

ISB 1302 is administered by intravenous (IV) infusion on Day 1, Day 8, Day 15, and Day 22 of each 28-day treatment cycle at dose levels. Dose on D1, D8, D15, D22 is 250 ng/kg

BIOLOGICALISB 1302 325 ng/kg

ISB 1302 is administered by intravenous (IV) infusion on Day 1, Day 8, Day 15, and Day 22 of each 28-day treatment cycle at dose levels. Dose on D1, D8, D15, D22 is 325 ng/kg

BIOLOGICALISB 1302 325 ng/kg-D1;425 ng/kg -D8,D15,D22

ISB 1302 is administered by intravenous (IV) infusion on Day 1, Day 8, Day 15, and Day 22 of each 28-day treatment cycle at escalating dose levels. Dose of ISB 1302 is 325 ng/kg on D1 and 425 ng/kg on D8, D15, D22

BIOLOGICALISB 1302 325 ng/kg-D1;550 ng/kg -D8,D15,D22

BIOLOGICALISB 1302 325ng/kgD1;550 ng/kg D8;700 ng/kgD15,22

BIOLOGICALISB 1302 325ng/kg D1;550 ng/kg D8;900 ng/kg D15,22

BIOLOGICALISB 1302 escalating doses,1200 ng/kg D15,22

BIOLOGICALISB 1302 at the MTD and/or RP2D dose

ISB 1302 at the MTD and/or RP2D dose in separate groups in the Q1W and/or the Q2W dose regimen.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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.	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.	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	RP2D: Incidence and severity of AEs, AESI, and SAEs, including but not limited to laboratory values, PK and biomarkers.
Anti-tumor Activity of ISB 1302 administered Q1W (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	Tumor Response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) (Part 2)

Secondary

Measure	Time frame	Description
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	PK parameter: Cmax - maximum observed serum concentration is estimated
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	PK parameter: tmax - time at which Cmax is observed
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	PK parameter: AUC0-tau - Area under the serum concentration-time curve over a dosing interval is estimated.
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	PK parameter: AUC0-t - Area under the serum concentration-time curve over the time interval from zero to last quantifiable concentration is estimated.
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	Percent incidence of antidrug antibodies (ADA) formation assessed from baseline until end of treatment (EOT)
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	Levels of cytokines, including IL-2 will be measured in peripheral blood as part of the pharmacodynamics and safety assessment to monitor for any signs of cytokine release syndrome.
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	Levels of cytokines, including IL-6 will be measured in peripheral blood as part of the pharmacodynamics and safety assessment to monitor for any signs of cytokine release syndrome.
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	Levels of cytokines, including IL-10 will be measured in peripheral blood as part of the pharmacodynamics and safety assessment to monitor for any signs of cytokine release syndrome.
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	Levels of cytokines, including IFN-γ will be measured in peripheral blood as part of the pharmacodynamics and safety assessment to monitor for any signs of cytokine release syndrome.
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	Levels of cytokines, including TNF-α, will be measured in peripheral blood as part of the pharmacodynamics and safety assessment to monitor for any signs of cytokine release syndrome.
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	Cellular biomarkers to be analyzed include CD3 will be assessed by fluorescence activated cell sorting (FACS) analysis of peripheral blood leucocytes as surrogate markers for ISB 1302 activity
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	Cellular biomarkers to be analyzed include CD4 will be assessed by fluorescence activated cell sorting (FACS) analysis of peripheral blood leucocytes as surrogate markers for ISB 1302 activity
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	Incidence, nature, and intensity of AEs according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
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	Cellular biomarkers to be analyzed include CD25 will be assessed by fluorescence activated cell sorting (FACS) analysis of peripheral blood leucocytes as surrogate markers for ISB 1302 activity
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	Cellular biomarkers to be analyzed include CD69 will be assessed by fluorescence activated cell sorting (FACS) analysis of peripheral blood leucocytes as surrogate markers for ISB 1302 activity
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	Cellular biomarkers to be analyzed include CD127 will be assessed by fluorescence activated cell sorting (FACS) analysis of peripheral blood leucocytes as surrogate markers for ISB 1302 activity
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	Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include T cells
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	Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include tumor microenvironment markers
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	Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include apoptotic markers
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	Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include Tumor Mutational Burden (TMB)
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	Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include Epigenetic evaluation of Tregs
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	Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include Epigenetic evaluation of T helper cells
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	Tumor response per RECIST v1.1 and iRECIST
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	Tumor Response per RECIST v1.1 and iRECIST
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	Cellular biomarkers to be analyzed include CD8 will be assessed by fluorescence activated cell sorting (FACS) analysis of peripheral blood leucocytes as surrogate markers for ISB 1302 activity
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	Tumor Response per RECIST v1.1.
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	Tumor Response per RECIST v1.1

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026