A Phase I Trial of CCT303-406 in Patients With Relapsed or Refractory HER2 Positive Solid Tumors

NCT04511871 | Active Not Recruiting Phase 1

• 1 other identifier: CCT303-406-mST01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical study is to investigate the safety and tolerability of CCT303-406 CAR modified autologous T cells (CCT303-406) in subjects with relapsed or refractory stage IV metastatic HER2-positive solid tumors.

Conditions

Solid Tumor; Gastric Cancer; Breast Cancer; Ovarian Cancer; Sarcoma

Keywords

HER2; CAR-T; Solid tumors

Outcome Measures

Primary Outcomes (1)

• MTD: to determine the maximum tolerated dose of CCT303-406

  To assess the DLT (dose limiting toxicities) attributed to CCT303-406 per cohort and determine the RP2D (recommended phase 2 dose).

  28 days following infusion

Secondary Outcomes (8)

• ORR (overall response rate): Proportion of subjects with the best overall response (BOR)

  Up to 52 weeks

• 12 month survival rate

  Up to 52 weeks

• DCR: Disease control rate

  Up to 52 weeks

• DOR: Duration of reponse

  Up to 52 weeks

• PFS: Progression free survival

  Up to 52 weeks

Other Outcomes (1)

• Exploration of target-efficacy correlation

  Up to 52 weeks

Study Arms (1)

CCT303-406

EXPERIMENTAL

To determine the safety, tolerability, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of CCT303-406 cell therapy in patients with HER2-positive (IHC 3+ in ≥50% tumor cells) relapsed or refractory solid tumors. Dose cohorts: * Dose 1: 3x10\^5 CCT303-406 CAR-positive T cells/kg body weight, intravenous infusion * Dose 2: 1x10\^6 CCT303-406 CAR-positive T cells/kg body weight, intravenous infusion * Dose 3: 1x10\^7 CCT303-406 CAR-positive T cells/kg body weight, intravenous infusion

Biological: CCT303-406

Interventions

CCT303-406 BIOLOGICAL

Blood will be collected from subjects to isolate peripheral blood mononuclear cells for the production of CCT303-406. Subjects will receive the conditioning chemotherapy regimen of cyclophosphamide and fludarabine for lymphodepletion followed by a single dose of CCT303-406 via intravenous injection.

CCT303-406

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with willingness to be in the study and follow all study procedures, and capable of providing informed consent
• Male or female aged 18-70 years
• Patients with stage IV (according to the 8th edition of AJCC) advanced solid tumor malignancies that have failed standard treatment of relapsed or difficult-to-treat solid tumors confirmed by histology or cytology
• At least one measurable lesion, i.e. the length of non-lymph node lesions examined according to CT cross-sectional scanning or magnetic resonance imaging (MRI), or the short diameter of the lymph node lesions is ≥15 mm according to RECIST 1.1
• Tumors with HER2 IHC 3+ in≥50% of all tumor cells as determined by IHC according to the Breast Cancer HER2 Testing (2019 edition) and the Gastric Cancer HER2 Testing (2016 edition); For HER2 IHC 3+ tumors other than gastric and breast cancers, FISH is required to confirm HER2 expression; For relapsed patients after HER2-targeted therapies, biopsy and IHC are required to confirm HER2 expression per enrollment criteria.
• ECOG Performance Status 0-1
• Expected survival greater than 12 weeks
• Adequate organ and hematopoietic system functions to meet the following requirements:
• Hemoglobin (HGB) s 90 g/L, no blood transfusions within two weeks;
• White blood cell (WBC) count≥2.5×109/L
• Absolute Neutrophil Count (ANC) ≥1.5 x 109/L
• Platelet (PLT) count ≥80-109/L
• Total bilirubin (TBIL) ≤3.0ng/dL or ≤5 ULN
• ALT and AST ≤5 ULN; for liver metastasis, ALT and AST ≤5 ULN
• Creatinine (Cr) ≤1.5 x ULN; or creatinine removal rate (CrCl) ≥50 mL/min

You may not qualify if:

• Females with pregnancy or in lactation period
• Patients with active hepatitis B, or active hepatitis C
• HIV positive
• Other active infections of clinical significance
• Patients receiving in situ surgery within 3 months
• Patients with the following previous or accompanying diseases:
• Patients diagnosed as severe autoimmune diseases that require long term (more than 2 months) treatment with systemic immunosuppressants (steroids), or diseases with immune-mediated symptoms, including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), and autoimmune vasculitis
• Patients with ≥Grade 2 peripheral neuronal diseases (according to NCI-CTCAE v5.0)
• Patients with any mental illness, including dementia, mental changes, which may cause difficulties understanding the informed consent and related questionnaires
• Patients with serious uncontrollable diseases, which may interfere with the therapies in this study
• Patients with other active malignancies in the past 5 years excluding those with completely cured basal or squamous skin cancers, superficial bladder cancers or primary breast cancers without need of follow-up treatment
• Patients receiving systemic steroids or steroid inhalants
• Patients who have received tumor immunotherapy (including monoclonal antibody or cell therapy) in the past 4 weeks
• Patients allergic to immunotherapies or related drugs
• Patients with metastatic lesions in meninges or central nervous system, or clear evidence of central nervous system diseases with continous significant symptoms in the last 6 months

Sponsors & Collaborators

• Shanghai PerHum Therapeutics Co., Ltd.: lead
• Shanghai Zhongshan Hospital: collaborator

Study Sites (1)

Zhongshan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Stomach Neoplasms; Breast Neoplasms; Ovarian Neoplasms; Sarcoma

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2020
• First Posted: August 13, 2020
• Study Start: July 9, 2020
• Primary Completion: October 24, 2024
• Study Completion: March 29, 2025
• Last Updated: October 28, 2024

Record last verified: 2024-10

Locations

CN (1)