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  • Medicine  (9)
  • XA 52760  (9)
  • 1
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    An oral methionine aminopeptidase II inhibitor for high-risk non-muscle invasive bladder cancer relapsed after intravesical therapies: Update of a phase II trial.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 6_suppl ( 2017-02-20), p. 303-303
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 6_suppl ( 2017-02-20), p. 303-303
    Abstract: 303 Background: In 2016, we reported the preliminary results of APL-1202, an oral MetAP2 inhibitor, in the first 18 patients enrolled in the phase II trial. The purpose of the present study is to update the results of efficacy, safety, pharmacokinetics at steady state and translational studies in 41 patients. Methods: This is an open-label, single-arm phase II trial conducted in 15 hospitals in China. High-risk in recurrence is defined according to EORTC recurrence score and probability tables in EAU 2012 Guidelines on NMIBC. The primary end point is the recurrence-free survival rate at 1 year. Plasma and urine samples at steady state were collected for pharmacokinetic studies, and separate plasma samples were collected for translational studies. Results: From May 2014, a total of 41 patients have been enrolled in this study, including 39 relapsed after intravesical chemotherapies only (chemo-failed subgroup), and 2 after both chemo and BCG treatments (BCG-failed subgroup). All of patients had TaT1 papillary tumors, and 3 with concurrent carcinoma in situ . APL-1202 did not cause any drug-related SAEs. By the time of this abstract submission, the 1-year recurrence-free rate is 54.3% (37.2-73.2%, 95% Confidence Interval) with a median recurrence-free survival of 14.7 months. APL-1202’s plasma exposure at steady state appears to increase proportionally to the increase of doses. Conclusions: APL-1202 is safe and well tolerated at a daily dose up to 750mg, TID, for 12 weeks followed by 3 months on-and-off in patients with recurred high-risk NMIBC. According to the EAU 2012 Guidelines on NMIBC, naïve high-risk NMIBC patients treated by intravesical chemotherapies have a 1-year recurrence-free rate of 39% (33-45%, 95% CI) with a median recurrence-free survival of 9 months. Our results support the concept that oral MetAP2 inhibitor APL-1202 as a second-line therapy has the potential to achieve at least similar efficacy with the first-line intravesical chemotherapies, and warrant a randomized trial alone or in combination with other therapies in NMIBC patients. Clinical trial information: CTR20131716.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.6_suppl.303
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Comparison of 3 PCR-based assays for microsatellite instability detection in formalin-fixed paraffin-embedded tissues of patients with colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e15042-e15042
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15042-e15042
    Abstract: e15042 Background: Routine assessment of microsatellite instability (MSI) status in colorectal cancer (CRC) patients can help with initial screening for Lynch syndrome, prediction of tumor prognosis and selection of patients for immunotherapy. Immunohistochemistry (IHC) and PCR-based approaches represent the current clinical laboratory standard for the evaluation of MSI status. Both Bethesda and Promega marker panels have been used widely in the world and the Bethesda panel and the six mononucleotides panel (NR21/BAT25/NR24/NR27/MONO27/BAT26) have been approved by the National Medical Products Administration (NMPA) in China. The Idylla MSI Test, a fully automated system based on real-time PCR, which incorporates 7 novel MSI loci (ACVR2A/BTBD7/DIDO1/MRE11/RYR3/SEC31A/SULF2) can perform MSI analysis within 150min using 1-3 tissue slides. The aim of this study was to evaluate the performance of the three 3 PCR-based assays for MSI detection including Idylla MSI Test, Bethesda and that six mononucleotides panel. Methods: One hundred and fifty-three formalin-fixed paraffin-embedded (FFPE) tumor tissues from patients with CRC were collected and their MSI status were analyzed using 3 PCR-based assays, respectively, i.e. the Idylla MSI, “2B3D” NCI panel and the six mononucleotides panel. All samples were previously evaluated by IHC method. Results: In the all 153 patients, IHC identified 27 cases to be MMR-deficient (dMMR), and 126 to be MMR-proficient (pMMR). Using IHC as a reference, the Idylla MSI had a higher consistency that showed overall agreement, sensitivity and specificity as 93.46%, 92.89% and 93.65%, respectively, while the corresponding values of the six mononucleotides panel were 84.31%, 92.59% and 82.54% respectively, and the “2B3D” NCI panel showed a sensitivity of 92.16%, a specificity of 88.89% and an overall concordance of 92.86%. The PCR-based approaches identified 11 more MSI-H cases than IHC while 22 dMMR cases identified by IHC were detected by all the 3 assays, 2 dMMR by 2 assays, 1 dMMR by one assay only and 1 dMMR by neither assays above. Moreover, the Idylla MSI showed advantages in ease of use, turnaround time (TAT) and small dose of tissue input. Conclusions: Our findings support that the Idylla MSI assay provides a rapid, reliable, and ease-to-use solution to MSI detection in Chinese CRC patients with high sensitivity and specificity. The inconsistent cases between IHC and PCR-based approaches need a further analysis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e15042
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
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    BRAF fusion in lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21598-e21598
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21598-e21598
    Abstract: e21598 Background: BRAF was a part of RAS/MAPK pathway, which regulated the proliferation, differentiation, migration, and apoptosis of cells. BRAF V600E was a potential treatment target for non-small cell lung cancer and other tumors. While BRAF fusion was rare in lung cancer. Here we focus on BRAF fusion in lung cancer. Methods: We retrospectively reviewed next-generation sequencing (NGS) results of lung cancers, with or without treatment history. The samples were subjected to NGS using 59 or 1021-gene panel, which enables simultaneously assess snv, indel, rearrangements and cnv variations. Patients with BRAF fusion were collected and used to analysis. Results: We found eighteen lung cancers have BRAF fusion from about twelve thousand patients, 13 are females. The median age at diagnosis was 47-year old (range 28 to 70). Tested samples included 13 tissues, 5 plasma, and 2 pleural effusion. BRAF fusion could occur in different stage, 12 stage Ⅳ and 1 stage Ⅰ, other were unknown. There were 14 lung adenocarcinoma, 1 squamous cell carcinoma and 1 adenosquamous carcinoma, other two patients were unknown. The partner genes of BRAF fusion were distinctly among the patient, TRIM24 was relatively common. The median tumor mutation burden (TMB) was 4.8muts/Mb (range 0 to 15.4), with low TMB-H frequency (10.5%, defined 9 as cutoff value). Seven patients had no system treatment history, and 1 had concurrent EGFR L858R mutation. Nine patients received EGFR-TKI therapy, 1 received ALK-TKI therapy, and 1 received chemotherapy. Among the EGFR-TKI treated patients, 7 received first and third generation TKI sequential therapy, the median TTD (time to discontinue) of TKIs was 26 months (range 17 to 46). The EGFR mutation still exist when EGFR-TKIs resistance, included EGFR primary mutation, T790M, and C797S, concurrent with BRAF fusion. Except for BRAF fusion, there also had other complex resistance mechanism occurred, like HER2 mutation, KRAS mutation, etc. Conclusions: BRAF fusion had low frequency in lung cancer and occurred at different stage during disease development. BRAF inhibitors maybe a potential strategy for BRAF fusion lung cancers. As TKIs resistance mechanism, BRAF fusion is a huge clinical challenge, indicate the importance of further research.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e21598
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 4
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    A multi-center, randomized, prospective study evaluating the optimal radiation dose of definitive concurrent chemoradiation for inoperable esophageal squamous cell carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. 4013-4013
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 4013-4013
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.4013
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Anti-LAG-3 antibody LBL-007 in combination with toripalimab in patients with unresectable or metastatic melanoma: A phase Ⅰ, open-label, multicenter, dose escalation/expansion study.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 9538-9538
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 9538-9538
    Abstract: 9538 Background: LBL007 is a novel, fully human IgG4 monoclonal antibody targeting human Lymphocyte-activation gene3 (LAG-3). Dual inhibition of anti-programmed cell death protein 1 (PD-1) and LAG-3 is anticipated to synergistically increase immune response against tumor growth. Here we report the preliminary safety and efficacy of LBL-007 in combination with Toripalimab (an anti-PD-1 antibody has approved for treatment of melanoma in China) in patients (pts) with unresectable or metastatic melanoma. Methods: Pts with unresectable or metastatic melanoma with or without prior anti-PD-(L)1 therapy were enrolled. This trial comprised 2 parts, namely part 1 (dose escalation), pts received LBL-007 (0.25/1/3/6 mg/kg) /Toripalimab (3 mg/kg) both i.v., Q2W; and part 2 (expansion), pts received LBL-007 (3/6 mg/kg)/Toripalimab (3 mg/kg) both i.v., Q2W. The primary objective was safety, the second objectives included pharmacokinetics, pharmacodynamics and efficacy (per RECIST 1.1). Results: By Jan 2022, 37 pts (15 [40.5%] male, median age 59 [range 31-74] years, 9 pts [24.3%] with baseline LDH elevation, 18 [48.6%] with acral, 12 [32.4%] mucosal, 5 [13.5%] nonacral cutaneous, 2 [5.4%] primary site unknown) were enrolled, with 17 in part 1 and 20 in part 2. No dose-limiting toxicity was observed in part 1, and the MTD was not reached. Of all 37 pts, the most common treatment-emergent adverse events (TEAEs) included anemia (24.3%), creatine phosphokinase elevation (24.3%), hypothyroidism (21.6%), and aspartate aminotransferase elevation (21.6%). For 32 radiologically evaluable pts, ORR was 12.5%, DCR was 53.1%. In a preplanned subtype-specific analysis in anti-PD-(L)1 treatment-naïve pts, ORR was 27.3 % vs. 0%, and DCR was 81.8% vs. 50.0% in acral and mucosal melanoma subtypes, respectively. For anti-PD-(L)1-resistant pts (n = 11), DCR was 18.2%. Conclusions: LBL007/Toripalimab combination is well tolerated and promising efficacy in pts with unresectable or metastatic melanoma, especially in the acral type without prior anti-PD-(L)1 therapy. Clinical trial information: NCT04640545.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.9538
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Pathogenic germline mutation profile in Chinese lung cancers and related-driver mutation pattern.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e13003-e13003
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13003-e13003
    Abstract: e13003 Background: Many cancers could be driven by germline mutation exampled as BRCA1/2 in breast or ovarian cancer. However, the candidate predisposition variants for Chinese lung cancer are largely unknown. Methods: We reviewed 1797 Chinese lung cancer patients with paired tumor-normal samples sequenced by a 1021 gene panel. The annotation of germline variants within 95 selected susceptible genes was based on ACMG 2015 version guideline. Results: The frequency of patients identified with pathogenic or likely pathogenic (P/LP) germline variants were 5.95% (107 in 1797), which elevated to 10.1% (9 in 89) in patients younger than 40. Totally, 112 mutations from 35 genes were screened out. Recurrent pathogenic germline genes were BRCA2 (n = 14), FANCA (n = 9), RAD51D (n = 7), MUTYH (n = 7), ATM (n = 7) and TP53 (n = 5). The average age at diagnosis was numerically 2 years earlier in patients with P/LP (mean, 58.2 vs. 60.0, p = 0.22) than other patients without significance, but different genes contribute to discordant effects. Significantly early onset age was found in germline BRCA1/ 2 mutation (median, 52.5 versus 60.0 yrs in patients without P/LP, p = 0.0080) while later onset age was associated with germline PMS2 mutation (median, 74 versus 60.0 yrs, p = 0.0214 ). In terms of clinical actionable somatic mutation, the frequency of KRAS (15/89, 16.85% versus 121/1429, 8.47%, p = 0.012) and c-MET (6/89, 6.74% versus 31/1429, 2.17%, p = 0.018) in germline mutant patients were significantly higher, while TP53 (41/89, 46.07% versus 847/1429, 59.27%, p = 0.019) was apparently less mutated in P/LP lung cancer. As for frequency of EGFR, ALK, ROS-1, RET and BRAF, mutation frequency were not significantly different in lung cancer with germline mutation. Conclusions: Our study delineated the pathogenic germline mutation landscape in Chinese lung cancers for the first time. Predisposition genes demonstrated clinical actionable roles in onset age and therapeutic interventions. Further follow up may clarify the contribution of germline mutation to somatic mutation driven targeted therapy response and prognosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e13003
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 7
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    A phase 1 dose escalation study of GCC19CART: A novel coupled CAR therapy for patients with metastatic colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 3547-3547
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 3547-3547
    Abstract: 3547 Background: GCC19CART, the first clinical candidate from the CoupledCAR solid tumor platform, is designed to overcome the limitations of conventional CAR T-cells in solid tumor malignancies by pairing solid tumor CAR T-cells with CD19 targeting CAR T-cells to amplify the proliferation and activation of the solid tumor CAR T component. GCC19CART targets guanylate cyclase-C (GCC), which is expressed in the metastatic lesions of 70%-80% of subjects with colorectal cancers and largely restricted to the intestinal tract. A Phase 1 investigator-initiated clinical trial is underway in China for patients with relapsed or refractory metastatic colorectal cancer who have received at least 2 prior lines of therapy. As of a data cutoff on Jan 28, 2023 21 subjects have been enrolled in 2 dose escalation groups at 5 hospitals in China. Methods: Subjects are screened for GCC expression by immunohistochemistry. Eligible subjects undergo leukapheresis, a single dose of lymphodepleting chemotherapy (fludarabine 30mg/m 2 and cyclophosphamide 300mg/m 2 ) 3 days prior to infusion, and then administration of a single infusion of GCC19CART at one of two preassigned doses: 1x10 6 or 2x10 6 CAR T-cells/kg. All responses were confirmed by an independent third-party imaging contract research organization. Results: 13 subjects have been enrolled to dose level 1 (1x10 6 cells/kg) and 8 subjects have been enrolled to dose level 2 (2x10 6 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, overall response rate (ORR) 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 was 50% (4/8). 4 subjects demonstrated a PR and 2 additional subjects had PMR on PET/CT with SD per RECIST 1.1.The median PFS was 1.9 months in the dose 1 group and 6.3 months in the dose 2 group. The median overall survival was 13.3 months in the dose 1 group and 18.3 months in the dose 2 group. 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. Clinical trial information: ChiCTR2000040645 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.3547
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Updated safety and efficacy results from the phase I study of either LBL-007 (an anti-LAG-3 antibody) in combination with toripalimab (an anti-PD-1 antibody) or LBL-007 in combination with toripalimab and axitinib in patients with advanced melanoma.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 9541-9541
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 9541-9541
    Abstract: 9541 Background: Initial safety and efficacy data of LBL-007 plus toripalimab in patients with advanced melanoma (Part A) have been reported in 2022 ASCO (Abstract 9538). Here we present the updated results of part A and the preliminary results of part B (LBL-007 plus toripalimab with axitinib). Median follow-up was 9.7 months at cut-off data (January 11, 2023). Methods: Patients with advanced melanoma with or without prior therapy were enrolled during Jan 2021 - Aug 2022. This trial comprised 2 parts: Part A, patients received LBL-007 (0.25 - 10 mg/kg for dose escalation; 3 or 6 mg/kg for dose expansion) plus toripalimab at 3 mg/kg (both i.v. Q2W); and Part B, patients received LBL-007 at 3 or 6 mg/kg plus toripalimab at 3 mg/kg (both i.v. Q2W) and axitinib at 5 mg BID. The primary objective was safety, the second objectives were pharmacokinetics, pharmacodynamics and efficacy (per RECIST v.1.1). Results: In part A, 68 patients in total (57 treatment-naïve) were enrolled including 20 patients in dose escalation and 48 patients in dose expansion, and among which, 31 additional patients have been enrolled since 2022 ASCO report. Nineteen (27.9%) patients occurred grade ≥3 TEAEs, the common grade ≥3 TEAEs was anaemia (11.8%). No new safety signals were detected. Among 55 efficacy evaluable treatment-naïve patients (41 with acral, 7 mucosal, 7 others), ORR was 23.6%, DCR was 58.2%, and mPFS was 5.7 months (95% CI: 3.7, 9.5). In part B, 11 patients (10 mucosal, 1 acral) were enrolled. No DLT was observed. Five patients (45.5%) occurred grade ≥3 TEAEs, the common grade ≥3 TEAEs included blood pressure increased (18.2%) and transaminases increased (18.2%). One (9.1%) patient discontinued treatment due to TEAEs. ORR was 45.4% (including 4 mucosal and 1 acral), DCR was 72.7%, and mPFS was 5.5 months (95% CI: 1.8, 9.1). Conclusions: LBL-007 plus toripalimab continued to show promising antitumor activity and manageable safety profile in patients with treatment-naïve melanoma, which support further development in this indication. LBL-007/toripalimab/axitinib combination demonstrated acceptable safety profile and encouraging antitumor activity in patients with mucosal melanoma. Acknowledgements: Junshi Biosciences. Clinical trial information: NCT04640545 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.9541
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 9
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    A phase 1 dose-escalation study of GCC19 CART a novel coupled CAR therapy for subjects with metastatic colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 3582-3582
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 3582-3582
    Abstract: 3582 Background: Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in hematologic malignancies but limited success in solid tumors. GCC19CART, the first clinical candidate from the CoupledCAR solid tumor platform, is designed to overcome the limitations of conventional CAR T-cells in solid tumor malignancies by pairing solid tumor CAR T-cells with CD19 targeting CAR T-cells to amplify proliferation and activation of the solid tumor CAR T component. GCC19CART targets guanylate cyclase-C (GCC) which is expressed in the metastatic lesions of 70%-80% of subjects with colorectal cancers. A Phase 1 investigator-initiated clinical trial is underway in China for patients with relapsed or refractory metastatic colorectal cancer who have received at least 2 prior lines of therapy. Based on a data cutoff on December 13, 2021, 21 subjects have been enrolled in 2 dose escalation groups at 5 hospitals in China. 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: 1x10 6 or 2x10 6 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 (1x10 6 cells/kg) and 8 subjects have been enrolled to dose level 2 (2x10 6 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%)). Neurotoxicity 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: GCC19CART demonstrated 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 United States based Phase 1 trial of GCC19CART is anticipated for mid-2022. Clinical trial information: ChiCTR2100053828.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.3582
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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