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644 A phase 1 dose escalation study of GCC19CART – A novel CoupledCAR® therapy for subjects with metastatic colorectal cancer
  1. Naifei Chen1,
  2. Chengfei Pu2,
  3. Lingling Zhao1,
  4. Ning Li3,
  5. Chang Wang1,
  6. Yusheng Huang4,
  7. Suxia Luo5,
  8. Xun Li6,
  9. Zhenzhou Yang7,
  10. Jun Bie8,
  11. Ruihong Zhu2,
  12. Xi Huang2,
  13. Haiyang Tang2,
  14. Tingting Liang1,
  15. Yizhuo Wang1,
  16. Beibei Jia2,
  17. Dongqi Chen2,
  18. Victor Lu9,
  19. Zhao Wu2,
  20. Yongping Song10,
  21. Lei Xiao9 and
  22. Jiuwei Cui11
  1. 1The First Bethune Hospital of Jilin University, Changchun, China
  2. 2Innovative Cellular Therapeutics, Shanghai, China
  3. 3Zhengzhou University, Zhengzhou, China
  4. 4The Second Affiliated Hospital of CQMU, Chongqing, China
  5. 5Henan Cancer Hospital, Zhengzhou, China
  6. 6The First Hospital of Lanzhou University, Lanzhou, China
  7. 7Chongqing Medical University, Shanghai, China
  8. 8Nanchong Central Hospital, Nanchong, China
  9. 9Innovative Cellular Therapeutics, Inc., Rockville, MD, USA
  10. 10Henan Cancer Hospital, Zhengzhou, China
  11. 11The First Hospital of Jilin University, Changchun, China


Background GCC19CART, the first clinical candidate from the CoupledCAR® solid tumor platform, targets guanylate cyclase-C (GCC) which is expressed in colorectal cancers. CoupledCAR utilizes multiple vectors to make both solid tumor targeting CAR-T and CD19 CAR-T in a single manufacturing step. An investigator-initiated dose escalation trial in China for patients with relapsed or refractory metastatic colorectal cancer (R/R mCRC) is reported here.

Methods Subjects are screened for GCC expression by immunohistochemistry. Eligible subjects undergo leukapheresis, a single dose of lymphodepleting chemotherapy (fludarabine 30mg/m2 and cyclophosphamide 300mg/m2) 3 days prior to infusion, and then administration of a single infusion of GCC19CART at one of two preassigned doses: 1x106 or 2x106 CAR T-cells/kg. Endpoints are safety and preliminary evidence of efficacy as determined by CT or PET/CT per RECIST 1.1 or PERCIST 1.0. All responses were confirmed by an independent third-party imaging contract research organization (CRO).

Results 13 subjects have been enrolled to dose level 1 (1x106 cells/kg) and 8 subjects have been enrolled to dose level 2 (2x106 cells/kg). The most common adverse events were cytokine release syndrome (CRS) in 21/21 subjects (Grade 1 19/21 (90.48%) or Grade 2 2/21 (9.52%)) and diarrhea in 21/21 subjects (Grade 1 6/21 (28.57%) Grade 2 5/21 (23.81%) Grade 3 9/21 (42.86%) or Grade 4 1/21 (4.76%)). All patients with grade 3 and higher side effects were well managed. Immune effector cell-associated neurotoxicity syndrome(ICANS) was observed in 2/21 (9.52%) subjects at Grade 3 or 4 and resolved with corticosteroids. The combined overall response rate (ORR) for both dose levels was 28.6% (6/21). For dose level 1, the overall response rate (ORR) per RECIST 1.1 was 15.4% (2/13). Two subjects demonstrated a partial response (PR) while 3 additional subjects had partial metabolic response (PMR) on PET/CT with stable disease (SD) or progressive disease (PD) per RECIST 1.1. For dose level 2, The ORR per RECIST 1.1 was 50% (4/8). 4 subjects demonstrated a PR (3 at month 1, 1 at month 3 after being SD at month 1) and 2 additional subjects had PMR on PET/CT with SD per RECIST 1.1.

Conclusions Preliminary results demonstrate that GCC19CART has meaningful dose-dependent clinical activity and an acceptable safety profile in relapsed or refractory metastatic colorectal cancer. This trial is ongoing and updated data will be presented. A Phase 1 trial of GCC19CART in the US has opened for accrual and is expected to enroll patients in mid-2022.

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