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

Primary Purpose

Breast Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ISB 1302 250 ng/kg

ISB 1302 325 ng/kg

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

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

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

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

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

ISB 1302 at the MTD and/or RP2D dose

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Breast Cancer, GBR 1302, HER2, HER2 x CD3 bispecific antibody, ISB 1302 (CD3 Bispecific Ab) in HER2-positive Metastatic Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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.

Sites / Locations

Ichnos Investigational Site 1
Ichnos Investigational Site 5
Ichnos Investigational Site 4
Ichnos Investigational Site 2
Ichnos Investigational Site 3

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

Part 1: Cohort 101 - ISB 1302 250 ng/kg

Part 1: Cohort 201 - ISB 1302 325 ng/kg

Part 1:Cohort 301- ISB 1302 325 ng/kg-D1;425 ng/kg -D8,D15,D22

Part 1:Cohort 401- ISB 1302 325 ng/kg-D1;550 ng/kg -D8,D15,D22

Part1Cohort501-ISB1302 325ng/kgD1;550 ng/kg D8;700 ng/kgD15,22

Part1Cohort601-ISB1302 325ng/kgD1;550 ng/kg D8;900 ng/kgD15,22

Part 1 Cohort 701- ISB 1302 escalating doses,1200 ng/kg D15,22

Part 2 (Dose Expansion) -ISB 1302 at the MTD and/or RP2D dose

Arm Description

Cohort 101, subjects will be administered ISB 1302 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

Cohort 201, subjects will be administered ISB 1302 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

Cohort 301, subjects will be administered ISB 1302 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 GBR 1302 is 325 ng/kg on D1 and 425 ng/kg on D8, D15, D22

Cohort 401, subjects will be administered ISB 1302 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

Cohort 501, subjects will be administered ISB 1302 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

Cohort 601, subjects will be administered ISB 1302 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

Cohort 701, subjects will be administered ISB 1302 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

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

Outcomes

Primary Outcome Measures

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.

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

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

Secondary Outcome Measures

Incidence, nature, and intensity of AEs according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Antitumor activity of ISB 1302 administered Q1W (Part 1)

Tumor Response per RECIST v1.1.

Additional preliminary anti-tumor clinical activity of ISB 1302 administered (Part 2)

Tumor Response per RECIST v1.1

Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) -Cmax

PK parameter: Cmax - maximum observed serum concentration is estimated

Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2)-tmax

PK parameter: tmax - time at which Cmax is observed

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.

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.

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)

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.

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.

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.

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IFN-γ

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

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

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

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

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

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

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

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

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

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

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

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)

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

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

Exploratory: Duration of treatment (Part 1 and Part 2)

Tumor response per RECIST v1.1 and iRECIST

Exploratory: Time to disease progression (Part 1 and Part 2)

Tumor Response per RECIST v1.1 and iRECIST

Full Information

NCT ID

NCT03983395

First Posted

May 31, 2019

Last Updated

May 19, 2021

Sponsor

Ichnos Sciences SA

Collaborators

Glenmark Pharmaceuticals S.A.

1. Study Identification

Unique Protocol Identification Number

NCT03983395

Brief Title

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

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Terminated

Why Stopped

The study was terminated during Part 1 (dose escalation), and Part 2 (expansion) of the study was not initiated. This study was voluntarily terminated due to a business decision not to proceed with the ISB 1302 asset, and not due to any safety issue.

Study Start Date

April 8, 2020 (Actual)

Primary Completion Date

July 24, 2020 (Actual)

Study Completion Date

July 24, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ichnos Sciences SA

Collaborators

Glenmark Pharmaceuticals S.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

Breast Cancer, GBR 1302, HER2, HER2 x CD3 bispecific antibody, ISB 1302 (CD3 Bispecific Ab) in HER2-positive Metastatic Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Cohort 101 - ISB 1302 250 ng/kg

Arm Type

Experimental

Arm Description

Arm Title

Part 1: Cohort 201 - ISB 1302 325 ng/kg

Arm Type

Experimental

Arm Description

Arm Title

Part 1:Cohort 301- ISB 1302 325 ng/kg-D1;425 ng/kg -D8,D15,D22

Arm Type

Experimental

Arm Description

Arm Title

Part 1:Cohort 401- ISB 1302 325 ng/kg-D1;550 ng/kg -D8,D15,D22

Arm Type

Experimental

Arm Description

Arm Title

Part1Cohort501-ISB1302 325ng/kgD1;550 ng/kg D8;700 ng/kgD15,22

Arm Type

Experimental

Arm Description

Arm Title

Part1Cohort601-ISB1302 325ng/kgD1;550 ng/kg D8;900 ng/kgD15,22

Arm Type

Experimental

Arm Description

Arm Title

Part 1 Cohort 701- ISB 1302 escalating doses,1200 ng/kg D15,22

Arm Type

Experimental

Arm Description

Arm Title

Part 2 (Dose Expansion) -ISB 1302 at the MTD and/or RP2D dose

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

ISB 1302 250 ng/kg

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

ISB 1302 325 ng/kg

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

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

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

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

Intervention Description

Intervention Type

Biological

Intervention Name(s)

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

Intervention Description

Intervention Type

Biological

Intervention Name(s)

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

Intervention Description

Intervention Type

Biological

Intervention Name(s)

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

Intervention Description

Intervention Type

Biological

Intervention Name(s)

ISB 1302 at the MTD and/or RP2D dose

Intervention Description

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

Primary Outcome Measure Information:

Title

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.

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.

Time Frame

28 days

Title

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

Description

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

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

Title

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

Description

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

Time Frame

Secondary Outcome Measure Information:

Title

Incidence, nature, and intensity of AEs according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Description

Incidence, nature, and intensity of AEs according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Time Frame

Title

Antitumor activity of ISB 1302 administered Q1W (Part 1)

Description

Tumor Response per RECIST v1.1.

Time Frame

Title

Additional preliminary anti-tumor clinical activity of ISB 1302 administered (Part 2)

Description

Tumor Response per RECIST v1.1

Time Frame

Title

Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) -Cmax

Description

PK parameter: Cmax - maximum observed serum concentration is estimated

Time Frame

Title

Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2)-tmax

Description

PK parameter: tmax - time at which Cmax is observed

Time Frame

Title

Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) -AUC0-tau

Description

PK parameter: AUC0-tau - Area under the serum concentration-time curve over a dosing interval is estimated.

Time Frame

Title

Pharmacokinetics of ISB 1302 administered Q1W (Part 1 and Part 2) - AUC0-t

Description

PK parameter: AUC0-t - Area under the serum concentration-time curve over the time interval from zero to last quantifiable concentration is estimated.

Time Frame

Title

Immunogenicity of ISB 1302 administered Q1W (Part 1 and Part 2)

Description

Percent incidence of antidrug antibodies (ADA) formation assessed from baseline until end of treatment (EOT)

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-2

Description

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.

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-6

Description

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.

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IL-10

Description

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.

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- IFN-γ

Description

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.

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) - levels of pharmacodynamic cytokines- TNF-α

Description

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.

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD3

Description

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

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD4

Description

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

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD8

Description

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

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD25

Description

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

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers -CD69

Description

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

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Pharmacodynamic Cellular Biomarkers - CD127

Description

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

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include T cells

Description

Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include T cells

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include tumor microenvironment markers

Description

Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include tumor microenvironment markers

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include apoptotic markers

Description

Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include apoptotic markers

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include Tumor Mutational Burden (TMB)

Description

Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include Tumor Mutational Burden (TMB)

Time Frame

Title

Exploratory: Pharmacodynamic biomarkers of ISB 1302 (Part 1 and Part 2) -Tumor tissue biopsy -Analyses of the tumor tissue include Epigenetic evaluation of Tregs

Description

Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include Epigenetic evaluation of Tregs

Time Frame

Title

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

Description

Descriptive statistics for pharmacodynamic biomarker assessments such as Tumor tissue biopsy - Analyses of the tumor tissue include Epigenetic evaluation of T helper cells

Time Frame

Title

Exploratory: Duration of treatment (Part 1 and Part 2)

Description

Tumor response per RECIST v1.1 and iRECIST

Time Frame

Title

Exploratory: Time to disease progression (Part 1 and Part 2)

Description

Tumor Response per RECIST v1.1 and iRECIST

Time Frame

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Facility Information:

Facility Name

Ichnos Investigational Site 1

City

Gilbert

State/Province

Arizona

ZIP/Postal Code

85234

Country

United States

Facility Name

Ichnos Investigational Site 5

City

Los Angeles

State/Province

California

ZIP/Postal Code

90048

Country

United States

Facility Name

Ichnos Investigational Site 4

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40212

Country

United States

Facility Name

Ichnos Investigational Site 2

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Ichnos Investigational Site 3

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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