Autologous huMNC2-CAR44 or huMNC2-CAR22 T Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*)

NCT04020575 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 10038
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I/II study of adoptive immunotherapy for advanced MUC1\* positive breast cancer with autologous T cells engineered to express either a chimeric antigen receptor, huMNC2-CAR44 or huMNC2-CAR22, which are specific for a cleaved form of MUC1 (MUC1\*).

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events

  To determine the safety and maximally tolerated cell dose (MTD) and recommended phase 2 cell dose (RP2D) of ex vivo expanded autologous huMNC2-CAR44 T cells or huMNC2-CAR22 CAR T cells for patients with advanced MUC1\* positive breast cancer using CTCAE version 5.0 and Lee criteria.

  Within 35 days after T cell infusion

Secondary Outcomes (3)

• In vivo persistence

  Up to 365 days after the T cell infusion

• Preliminary Antitumor Activity

  Up to 15 years

• Antitumor Activity

  Up to 15 years

Study Arms (4)

Dose Escalation

EXPERIMENTAL

Dose escalation or de-escalation is tested in cohorts of 3 patients each using standard "3+3" dose-finding.

Biological: huMNC2-CAR44 CAR T cells or huMNC2-CAR22 CAR T cells

Luminal

EXPERIMENTAL

Dose Expansion - 15 patients will be enrolled with luminal (hormone receptor positive, HER2 negative) metastatic breast cancer.

Biological: huMNC2-CAR44 CAR T cells or huMNC2-CAR22 CAR T cells @ RP2D

HER2+

EXPERIMENTAL

Dose Expansion - 15 patients will be enrolled with HER2+ metastatic breast cancer.

Biological: huMNC2-CAR44 CAR T cells or huMNC2-CAR22 CAR T cells @ RP2D

Triple Negative

EXPERIMENTAL

Dose Expansion - 15 patients will be enrolled with triple negative metastatic breast cancer.

Biological: huMNC2-CAR44 CAR T cells or huMNC2-CAR22 CAR T cells @ RP2D

Interventions

huMNC2-CAR44 CAR T cells or huMNC2-CAR22 CAR T cells BIOLOGICAL

huMNC2-CAR44 T cells or huMNC2-CAR22 CAR T cells are an autologous T cell product transduced with a proprietary lentiviral vector backbone coding for humanized MNC2-scFv (the targeting head).

Dose Escalation

huMNC2-CAR44 CAR T cells or huMNC2-CAR22 CAR T cells @ RP2D BIOLOGICAL

huMNC2-CAR44 T cells or huMNC2-CAR22 CAR T cells are an autologous T cell product transduced with a proprietary lentiviral vector backbone coding for humanized MNC2-scFv (the targeting head) @ RP2D

HER2+; Luminal; Triple Negative

Eligibility Criteria

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

You may qualify if:

• Confirmation of diagnosis of breast cancer by pathology review of initial or subsequent biopsy or other pathologic material at the City of Hope Pathology department. ER, PR, and HER2 status known and documented per ASCO/CAP guidelines.
• For dose expansion cohorts, tumors with ER and/or PR ≥1% will be considered hormone receptor positive. Tumors with ER and PR \<1% will be considered hormone receptor negative. HER2 status will be determined by IHC or FISH per ASCO/CAP guidelines. Patients will be allocated to expansion cohorts according to guidelines in table below.
• Dose expansion cohorts
• Expansion Cohort Hormone Receptor status HER2 status Luminal ER and/or PR \>/=1% positive Negative by IHC or FISH HER2 positive Any ER or PR status Positive by IHC or FISH Triple Negative ER and PR \<1% Negative by IHC or FISH
• Patients must have received standard metastatic systemic therapy per NCCN guidelines or institutional practice which are known to confer benefit. No maximum on number of prior systemic treatment regimens.
• Patients with hormone receptor positive disease must have received at least 3 prior endocrine therapies and at least 2 prior lines of chemotherapy in the metastatic setting.
• Patients with HER2 positive breast cancer must have received at least 3 prior HER2- directed therapies (trastuzumab, pertuzumab, TDM-1 or others) in the metastatic setting.
• Patients with triple negative disease must have received at least 2 prior lines of chemotherapy in the metastatic setting.
• MUC1\* membrane expression ≥30% by immunohistochemistry on a tumor specimen obtained at screening or previous tumor specimen that is less than 6-months old (see Appendix I for examples of MUC1\* expression patterns).
• Patients must be 18 years of age or older, of any gender, race or ethnicity.
• Patients must be capable of understanding and providing a written informed consent.
• Patients must have a Karnofsky performance status of ≥60%.
• Patients must have measurable disease by at least one of the criteria below:
• Extra skeletal disease that can be accurately measured by CT or MRI per RECIST 1.1,
• Skeletal or bone-only metastases measurable by FDG PET imaging.

You may not qualify if:

• Patients requiring ongoing daily corticosteroid therapy at a dose of \>15 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable.
• Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the PI.
• Major organ dysfunction defined as:
• Serum creatinine \> 2 mg/dL
• Bilirubin ≥ 1.5 mg/dL with the following exception: Patients with known Gilbert disease, serum bilirubin \> 3 mg/dL
• AST or ALT ≥ 2.5 x upper institutional limit of normal with the following exception: Patients with known hepatic metastases, AST or ALT \> 3x upper institutional limit of normal
• Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing. Those with an FEV1 of \< 50 % of predicted or DLCO (corrected) \< 40% will be excluded.
• Significant cardiovascular abnormalities as defined by any one of the following:
• i. NYHA class III or IV congestive heart failure, ii. clinically significant hypotension, iii. uncontrolled symptomatic coronary artery disease, or iv. a documented ejection fraction of \<45%. Any patient with an EF of 45-49% must receive clearance by a cardiologist to be eligible for the trial.
• ANC \<1000/mm\^3.
• Hemoglobin \<9 mg/dl (transfusion permitted to achieve this).
• Platelet count \<75,000/mm\^3.
• Treatment with investigational agent(s) within 30 days of planned lymphodepletion.
• HIV seropositive.
• Uncontrolled active infection.

Sponsors & Collaborators

• Minerva Biotechnologies Corporation: lead
• City of Hope Medical Center: collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010-3000, United States

RECRUITING

Related Publications (1)

• Gorodetska I, Samusieva A, Lahuta T, Ponomarova O, Socha O, Kozeretska I. Exploring New Frontiers: Alternative Breast Cancer Treatments Through Glycocalyx Research. Breast J. 2025 May 22;2025:9952727. doi: 10.1155/tbj/9952727. eCollection 2025.

  PMID: 40443562 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Joanne Mortimer, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joanne Mortimer, MD

CONTACT

1-800-826-4673; Minerva18625@coh.org

Study Design

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

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: July 16, 2019
• Study Start: January 15, 2020
• Primary Completion: January 1, 2025
• Study Completion (Estimated): January 15, 2035
• Last Updated: June 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)