The annual global oncology event – American Society of Clinical Oncology (ASCO) The annual meeting will be held from June 3 to June 7, 2022 local time. The treatment of gastric cancer/gastroesophageal junction cancer (GC/GEJC) has always been a hot spot. In recent years, the treatment strategy in this field has gradually developed from chemotherapy to targeted therapy, immunotherapy or combination therapy. At the same time, cellular immunotherapy ( Novel therapeutic strategies such as CAR-T), antibody drug conjugates (ADC) and bispecific antibodies are also shining. In this meeting, two studies respectively explored the Claudin18.2 (CLDN18.2) CAR-T cell CT041¹ and the HER2-targeting bispecific antibody KN026², fromBeijing Prof. Changsong Qi from the University Cancer Hospitaland Professor Jianming Xu from the Fifth Medical Center of the Chinese People’s Liberation Army General Hospital. Yimaitong organizes the research results as follows for readers.
Analysis of safety, tolerability and efficacy of CT041 in patients with advanced GC/GEJC: CT041 -Preliminary results of ST-01 trial
Research background
CLDN18.2 is usually expressed in gastric mucosa In the tight junction of GC/GEJC, some studies have confirmed that this protein also has a high expression level in GC/GEJC, and this target has become one of the therapeutic targets that has attracted much attention in the field of GC/GEJC. CT041 is a CLDN18.2-targeted CAR-T cell therapy. A phase I study demonstrated that CT041 was well tolerated and had significant clinical efficacy in CLDN18.2-positive, previously treated patients with advanced GC/GEJC . We conducted a phase Ib/II study, CT041-ST-01, and report here preliminary results of CT041 in patients with GC/EGCJ.
Methodology
This is an open-label, multicenter, Ib/II Phase 1 study to evaluate the safety, tolerability and efficacy of CT041 in patients with CLDN18.2 positive previously treated advanced GC/GEJC. The study includes a dose escalation/dose expansion phase (Phase Ib trial) and a safety/efficacy validation phase (Phase II trial). In the phase Ib trial phase, the investigators evaluated the two doses of 2.5*10⁸ and 3.75*10⁸ through a 3+3 study design. The main purpose of this phase is to evaluate the safety, tolerability of CT041, and to determine II Recommended Dosage for Phase 2 Studies (RP2D). Data as of December 22, 2021.
Study Results
From November 2020 to May 2021, the A total of 14 GC/GEJC patients were enrolled in Phase Ib. The median patient age was 44.5 years (range, 23-71 years), 85.7% of patients had received 2-line therapy, and 14.3% had received at least 3-line therapy; 57.1% had ≥3 organ metastases, and 92.9 Peritoneal metastasis was diagnosed in % of patients; signet ring cell carcinoma was present in 64.3% of patients. Three of the patients were treated with a dose of 3.75*10⁸ and 11 patients were treated with a dose of 2.5*10⁸ for up to three treatments.
The most common grade ≥3 adverse event in the study was hematologic toxicity related to lymphocyte depletion. No dose-limiting toxicities, treatment-related deaths, neurotoxicity, or gastrointestinal toxicity were observed. Cytokine release syndrome (CRS) occurred in most of the patients was grade 1 or 2, and 1 patient developed grade 4 CRS and recovered completely. At data cutoff, 8 of the 14 patients achieved partial response (PR) and 2 achieved stable disease (SD). The median follow-up time was 8.9 months (95%CI 5.91, NE), the median progression-free survival (PFS) was 5.6 months (95%CI 1.9, 7.4), and the median overall survival (OS) was 10.8 month (95% CI 5.1, NE), 7 patients were still alive at the last follow-up.
Conclusions
The preliminary results of this study suggest that the /GEJC patients, the safety and tolerability of CT041 are controllable and the efficacy is better. A Phase II trial of this study is ongoing and will further evaluate the clinical benefit of CT041.
Efficacy and safety of KN026 monotherapy in previously treated HER2-positive advanced GC/GEJC patients Sexual assessment
Research background
Second- and subsequent-line treatment outcomes in patients with advanced GC/GEJC are generally inconsistent Jia, how to improve this situation is the focus of the current research. KN026 is a novel HER2-targeting bispecific antibody, which is composed of trastuzumab and pertuzumab, which can simultaneously target HER2 in the near future. Membrane domain (IV) and dimerization domain (II). KN026 has demonstrated good antitumor efficacy in preclinical studies and phase I studies. Here, we report the efficacy and safety of KN026 monotherapy in previously treated patients with HER2-positive advanced GC/GEJC.
Methods
This is a multicenter, single-arm, open-label, In a dual-cohort phase II study, researchers divided patients with previously treated advanced GC/GEJC into either a HER2-high cohort (IHC 3+ or IHC 2+ISH+, cohort 1) or a HER2-low cohort (IHC 1+/2+ISH- or IHC 0/1+ISH+, cohort 2). KN026 at 10mg/kg QW or 20mg/kg Q2W or 30mg/kgThe dose of Q3W is administered intravenously. The primary endpoints were investigator-assessed objective response rate (ORR) and duration of response (DoR) according to RECIST 1.1. Secondary endpoints include progression-free survival (PFS), overall survival (OS) and safety.
Study Results
At the time of data cutoff on October 29, 2021, a total of Of 45 patients, 39 were assessed for disease response, 25 in cohort 1 and 14 in cohort 2.
The ORR of cohort 1 patients was 56% (95%CI 35%-76%), of which 14 patients were PR; median DoR was 9.7 months (95%CI 4.2-NE). Median follow-up of patients was 14.7 months (95%CI 9.4-16.5), median PFS was 8.3 months (95%CI 4.2-11.4), and median OS was 16.3 months (95%CI 11.0-NE) . In cohort 1, patients who had previously received trastuzumab therapy (n=14) had clinical benefits as shown in Table 1.
Table 1 Outcome analysis of patients previously treated with trastuzumab in cohort 1
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The ORR for cohort 2 patients was 14% (95%CI 2%-43%), and the median DoR was 6.2 months (95%CI 3.2 -NE). Median follow-up of patients was 27.5 months (95%CI 4.1-NE), median PFS was 1.4 months (95%CI 1.4-4.1), and median OS was 9.6 months (95%CI 3.5-14.9) .
A total of 37 patients experienced KN026-related adverse events (TRAEs), and the most common any-grade TRAE was increased aspartate aminotransferase (27 %), elevated alanine aminotransferase (20%), rash (16%), anemia (16%), and infusion-related reactions (16%). Five grade 3 TRAEs, including infusion-related reactions, hydronephrosis, ureteral stricture, elevated blood pressure, and abnormal liver function, occurred in 4 patients, with no grade 4 or 5 TRAEs.
Conclusions
KN026 as a single agent in previously treated patients with advanced GC/GEJC The therapy has shown good efficacy, and its toxicity is manageable, and further research is needed for follow-up evaluation of this therapy.
References:
1. Changsong QI, et al. Safety , tolerability, and preliminary efficacy results in patients with gastric/gastroesophageal junction adenocarcinoma from a phase Ib/II study of CLDN18.2 CAR T-cell therapy (CT041). J Clin Oncol 40, 2022 (suppl 16; abstr 4017)< /span>
2. Jianming Xu, et al. A phase II study evaluating KN026 monotherapy in patients (pts) with previously treated, advanced HER2-expressing gastric or gastroesophageal junction cancers (GC/GEJC ). J Clin Oncol 40, 2022 (suppl 16; abstr 4040)
Editor: Youshi
Type: Youshi
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