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

NCT03983395 | Terminated Phase 1 FDA Drug

• 2 other identifiers: ISB 1302-103IND Number 131316
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (27)

• 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

• 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

• 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

Study Arms (8)

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

EXPERIMENTAL

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

Biological: ISB 1302 250 ng/kg

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

EXPERIMENTAL

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

Biological: ISB 1302 325 ng/kg

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

EXPERIMENTAL

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

Biological: 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

EXPERIMENTAL

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

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

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

EXPERIMENTAL

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

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

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

EXPERIMENTAL

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

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

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

EXPERIMENTAL

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

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

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

EXPERIMENTAL

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

Biological: ISB 1302 at the MTD and/or RP2D dose

Interventions

ISB 1302 250 ng/kg BIOLOGICAL

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

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

ISB 1302 325 ng/kg BIOLOGICAL

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

ISB 1302 at the MTD and/or RP2D dose BIOLOGICAL

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

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

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ichnos Sciences SA: lead
• Glenmark Pharmaceuticals S.A.: collaborator

Study Sites (5)

Ichnos Investigational Site 1

Gilbert, Arizona, 85234, United States

Location

Ichnos Investigational Site 5

Los Angeles, California, 90048, United States

Location

Ichnos Investigational Site 4

Louisville, Kentucky, 40212, United States

Location

Ichnos Investigational Site 2

Detroit, Michigan, 48201, United States

Location

Ichnos Investigational Site 3

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2019
• First Posted: June 12, 2019
• Study Start: April 8, 2020
• Primary Completion: July 24, 2020
• Study Completion: July 24, 2020
• Last Updated: May 24, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)