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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03983395
• Other study ID #: ISB 1302-103
• Secondary ID: IND Number 13131
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 8, 2020
• Est. completion date: July 24, 2020

Study information

• Verified date: May 2021
• Source: Ichnos Sciences SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: July 24, 2020
• Est. primary completion date: July 24, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• ISB 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
• ISB 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
• ISB 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
• ISB 1302 325 ng/kg-D1;550 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 550 ng/kg on D8, D15, D22
• ISB 1302 325ng/kgD1;550 ng/kg D8;700 ng/kgD15,22
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 550 ng/kg on D8, and 700 ng/kg on D15, D22
• ISB 1302 325ng/kg D1;550 ng/kg D8;900 ng/kg D15,22
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 550 ng/kg on D8, and 900 ng/kg on D15, D22
• ISB 1302 escalating doses,1200 ng/kg D15,22
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 700 ng/kg on D8, and 1200 ng/kg on D15, D22
• ISB 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.

Locations

Country	Name	City	State
United States	Ichnos Investigational Site 2	Detroit	Michigan
United States	Ichnos Investigational Site 1	Gilbert	Arizona
United States	Ichnos Investigational Site 5	Los Angeles	California
United States	Ichnos Investigational Site 4	Louisville	Kentucky
United States	Ichnos Investigational Site 3	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Ichnos Sciences SA	Glenmark Pharmaceuticals S.A.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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
Primary	RP2D: Incidence and severity of AEs, AESI, and SAEs, including but not limited to laboratory values, PK and biomarkers.	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
Primary	Anti-tumor Activity of ISB 1302 administered Q1W (Part 2)	Tumor Response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) (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
Secondary	Incidence, nature, and intensity of AEs according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	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
Secondary	Antitumor activity of ISB 1302 administered Q1W (Part 1)	Tumor Response per RECIST v1.1.	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
Secondary	Additional preliminary anti-tumor clinical activity of ISB 1302 administered (Part 2)	Tumor Response per RECIST v1.1	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
Secondary	Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) -Cmax	PK parameter: Cmax - maximum observed serum concentration is estimated	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	Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2)-tmax	PK parameter: tmax - time at which Cmax is observed	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	Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) -AUC0-tau	PK parameter: AUC0-tau - Area under the serum concentration-time curve over a dosing interval is estimated.	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	Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) - AUC0-t	PK parameter: AUC0-t - Area under the serum concentration-time curve over the time interval from zero to last quantifiable concentration is estimated.	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	Immunogenicity of ISB 1302 administered Q1W (Part 1 and Part 2)	Percent incidence of antidrug antibodies (ADA) formation assessed from baseline until end of treatment (EOT)	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-2	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.	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-6	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.	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-10	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.	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IFN-?	Levels of cytokines, including IFN-? will be measured in peripheral blood as part of the pharmacodynamics and safety assessment to monitor for any signs of cytokine release syndrome.	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- TNF-a	Levels of cytokines, including TNF-a, will be measured in peripheral blood as part of the pharmacodynamics and safety assessment to monitor for any signs of cytokine release syndrome.	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD3	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	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD4	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	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD8	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	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD25	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	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD69	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	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers - CD127	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	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	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include T cells	Descriptive statistics for pharmacodynamic biomarker assessments such as 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
Secondary	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include tumor microenvironment markers	Descriptive statistics for pharmacodynamic biomarker assessments such as 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
Secondary	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include apoptotic markers	Descriptive statistics for pharmacodynamic biomarker assessments such as 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
Secondary	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include Tumor Mutational Burden (TMB)	Descriptive statistics for pharmacodynamic biomarker assessments such as 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
Secondary	Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include Epigenetic evaluation of Tregs	Descriptive statistics for pharmacodynamic biomarker assessments such as 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
Secondary	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	Descriptive statistics for pharmacodynamic biomarker assessments such as 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
Secondary	Exploratory: Duration of treatment (Part 1 and Part 2)	Tumor response per RECIST v1.1 and iRECIST	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	Exploratory: Time to disease progression (Part 1 and Part 2)	Tumor Response per RECIST v1.1 and iRECIST	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