A Phase I Trial of CCT303-406 in Patients With Relapsed or Refractory HER2 Positive Solid Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04511871|
Recruitment Status : Recruiting
First Posted : August 13, 2020
Last Update Posted : August 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor Gastric Cancer Breast Cancer Ovarian Cancer Sarcoma||Biological: CCT303-406||Phase 1|
This is a single arm, open label, dose escalation clinical study to evaluate the safety and preliminary therapeutic efficacy of CCT303-406 cells in adult subjects with HER2 positive relapsed or refractory stage IV metastatic solid tumors.
Subjects that meet inclusion criteria with positive biopsy HER2 (IHC 3+ in ≥50% tumor cells) will receive CCT303-406 according to the 3+3 dose escalation design.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial to Assess Safety, Tolerability and Anti-tumor Activity of Autologous T Cell Modified Chimeric Antigen Receptor (CAR) (CCT303-406) in Patients With Relapsed or Refractory HER2 Positive Solid Tumors|
|Actual Study Start Date :||July 9, 2020|
|Estimated Primary Completion Date :||March 3, 2022|
|Estimated Study Completion Date :||January 31, 2023|
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.
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.
- MTD: to determine the maximum tolerated dose of CCT303-406 [ Time Frame: 28 days following infusion ]To assess the DLT (dose limiting toxicities) attributed to CCT303-406 per cohort and determine the RP2D (recommended phase 2 dose).
- ORR (overall response rate): Proportion of subjects with the best overall response (BOR) [ Time Frame: Up to 52 weeks ]Best overall response (BOR) of subjects with PR (partial response) and CR (complete response) as determined by local investigator using RECIST 1.1
- 12 month survival rate [ Time Frame: Up to 52 weeks ]The proportion of living subjects within 52 weeks of infusion
- DCR: Disease control rate [ Time Frame: Up to 52 weeks ]The proportion of subjects with CR (complete response), PR (partial response) or SD (stable disease lasting over 6 months) as determined by local investigator using RECIST 1.1.
- DOR: Duration of reponse [ Time Frame: Up to 52 weeks ]The duration of time from record of response to first progression of disease as determined by RECIST 1.1 or death date not relevant to disease progression
- PFS: Progression free survival [ Time Frame: Up to 52 weeks ]The time of disease progression by RECIST 1.1 or death since cell infusion
- AE: Adverse Events [ Time Frame: Up to 52 weeks ]The incidence, severity and duration of AE, TEAE and SAE as determined by NCI-CTCAE v5.0
- The expansion over time of genetically modified CCT303-406 cells in the peripheral blood as determined by QPCR (copies/ug gDNA) [ Time Frame: Up to 52 weeks ]PK: Pharmacokinetics
- The persistence over time of genetically modified CCT303-406 cells in the peripheral blood as determined by Flow Cytometry (% CAR + cells) [ Time Frame: Up to 52 weeks ]PK: Pharmacokinetics
- Exploration of target-PK correlation [ Time Frame: Up to 52 weeks ]The correlation between levels of HER2 expression and CCT303-406 PK by QPCR.
- Exploration of target-efficacy correlation [ Time Frame: Up to 52 weeks ]The correlation between levels of HER2 expression and DCR and DOR
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04511871