The 2024 European Society for Medical Oncology (ESMO) Annual Meeting will be held in Barcelona, Spain, from September 13 to 17 local time. As one of the world's most important conferences in the field of oncology, ESMO will bring together oncology experts from all over the world to focus on the latest advances, cutting-edge technologies and clinical practices in oncology, disseminate cutting-edge information in the field of oncology to doctors, patients and the public, and promote the development of the field of oncology.
Esophageal cancer is one of the common malignant tumors with a high mortality rate worldwide, and although the application of immunotherapy and other regimens has improved the survival benefit of patients, there are still unmet patient needs in clinical practice, and new treatment strategies are urgently needed. In this conference, three studies by mainland scholars explored the application of novel therapeutic strategies such as bispecific antibodies, ADCs and immunomodulators in locally advanced unresectable esophageal cancer.
QL1706+根治性放化疗
Background:
For patients with inoperable locally advanced esophageal squamous cell carcinoma (ESCC), radical chemoradiotherapy is one of the standard treatment strategies. In recent years, immune checkpoint inhibitors, especially combined blockade of PD-1 and CTLA-4 pathways, have shown significant anti-tumor activity in a variety of cancer types. Previous studies have shown that PD-1 and CTLA-4 combined blockade has also shown good efficacy in advanced ESCC. Based on this, the investigators evaluated the safety and feasibility of dCRT in combination with QL1706 (PD-1/CTLA-4 combination antibody) as a first-line treatment for patients with locally advanced ESCC for the first time.
Research Methods:
This is an open-label, single-arm, single-center study with histologically confirmed locally advanced ESCC inclusion criteria in patients with locally advanced ESCC. All patients were treated with QL1706 and chemoradiotherapy at the same time, and the treatment strategy is shown in Figure 1. The primary endpoint of the study was progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), overall survival (OS), and safety.
Fig.1 Experimental design
Findings:
Between August 2022 and September 2023, a total of 39 patients were included in the study. The median age was 64 years (42-75 years) and 79.5% were male. Among them, 29 patients had stage III disease and 10 patients had stage IVa disease (see Table 1 for details). As of April 22, 2024, the median follow-up was 12.2 months.
Table 1 Baseline information of study subjects
The efficacy analysis showed that the 12-month PFS and OS rates were 62.1% and 86.2%, respectively. Median OS is immature. PFS was significantly longer in patients with PD-L1-positive tumors than in patients with PD-L1-negative tumors.
Safety analysis showed a 100% incidence of treatment-related adverse events (TRAEs) (Table 2). Grade ≥3 adverse events included lymphopenia (79.5%), leukopenia (46.2%), neutropenia (38.5%), thrombocytopenia (10.3%), anemia (7.7%), and pneumonia (5.1%). Two deaths occurred during the treatment period, one patient died of COVID-19 and the other died of upper gastrointestinal bleeding.
Table 2 Treatment-related adverse reactions
Conclusions of the study
First-line radical chemoradiotherapy combined with QL1706 in the treatment of ESCC has a controllable safety profile and good anti-tumor efficacy, which is worthy of further study. In the study population, the expression of PD-L1 has a strong predictive value.
BL-B01D1治疗局部晚期或转移性ESCC
Background:
BL-B01D1 is a bispecific ADC targeting EGFR and HER3. The study aims to explore the safety and efficacy of BL-B01D1 in the first-line treatment of ESCC.
Research Methods:
This is a phase I clinical study in patients with locally advanced or metastatic gastrointestinal cancer. In the dose expansion phase, the main treatment doses for enrolled ESCC patients were 2.0, 2.5, and 3.0 mg/kg, D1&D8, and Q3W. The experimental design is detailed in Figure 2.
Fig.2 Experimental design
Findings:
As of January 31, 2024, 83 previously treated patients with ESCC were enrolled, including 22 patients at a therapeutic dose of 2.0 mg/kg, 60 patients with a therapeutic dose of 2.5 mg/kg, and 1 patient with a therapeutic dose of 3.0 mg/kg. Of the enrolled ESCC patients, 94.0% (78/83) had received combination or sequential therapy with anti-PD-1/L1 and platinum agents. The median number of patients who received prior systemic therapy was 2 (range: 1-7 sessions), and the median follow-up for OS was 6.3 months. The baseline information of the enrolled patients is detailed in Table 3.
Table 3 Baseline characteristics of patients
The efficacy analysis showed that of the enrolled patients, 74 patients had an evaluable response. The ORR was 35.1% (26/74), the confirmed objective response rate (cORR) was 32.4% (24/74), the DCR was 73.6% (53/74), the median duration of response (mDOR) was 6.5 months, and the median PFS was 4.3 months (Table 4). For patients in the 2.5 mg/kg dose group, the ORR was 44.2% (23/52), the cORR was 40.4% (21/52), the DCR was 80.8% (42/52), the mDOR was 6.6 months, and the mPFS was 5.4 months (Table 4).
Table 4 Efficacy analysis
Safety analysis showed that the incidence of grade 3 TRAEs ≥in patients treated at a dose of 2.5 mg/kg was 53%, and the most common ≥ grade 3 TRAEs were anemia (25%), leukopenia (18%), thrombocytopenia (18%), neutropenia (15%), and lymphocyte count (15%) (Table 5). At the discretion of the investigator, a G3 grade interstitial lung disease (ILD) was observed. No new safety signals were observed.
Table 5 Security analysis
Conclusions of the study
In ESCC patients who have already received excessive pretreatment, BL-B01D1 exhibits a manageable safety profile and good anti-tumor activity. Further evaluation of the efficacy of BL-B01D1 in this patient population is ongoing.
AN002+根治性同步放化疗
Background:
AN0025 is a highly selective and potent antagonist against prostaglandin E2 receptor 4 (PGE2-EP4), which exerts anti-tumor effects by regulating the distribution and function of macrophages and immunosuppressive myeloid cells in the tumor microenvironment. The data show that ionizing radiation can induce apoptosis of tumor cells and promote the production of PGE2 in large quantities, so AN0025 combined with radiotherapy may synergistically exert anti-tumor effects, and has been confirmed in animal experiments and preclinical studies. In previous clinical studies, AN0025 combined with chemoradiotherapy has achieved good anti-tumor effects as a neoadjuvant treatment for locally advanced rectal cancer. Based on this, the investigators designed this study to evaluate the efficacy and safety of AN0025 in combination with chemoradiotherapy in patients with locally advanced unresectable esophageal cancer.
Research Methods:
This is a single-arm, open-label, multicenter, phase Ib study conducted in 3 centers in China, and the inclusion criteria of the study are patients with stage IVb/thoracic esophageal cancer with stage II-IVa or only supraclavicular lymph node metastases. The enrolled patients were all treated with AN0025 in combination with radical chemoradiotherapy, and from week 17 onwards, the patients received AN0025 monotherapy only at a dose level of 250 mg or 500 mg, and the treatment regimen is shown in Figure 1. The primary focus of the study is safety and tolerability, with secondary endpoints being anti-tumor efficacy, including ORR, DCR, PFS, and OS.
Fig.3 Experimental design
Findings:
As of April 25, 2024, a total of 12 patients were enrolled in the study, including 5 in the 250 mg dose group and 7 in the 500 mg dose group, with a median follow-up of 18.5 months, and the baseline characteristics of the patients are shown in Table 1.
Table 6 Baseline characteristics of patients
Efficacy analysis showed that of the 8 patients with measurable lesions at baseline, 1 (13%) achieved a confirmed complete response (CR) and 6 patients achieved a partial response (PR). The ORR was 88% and the confirmed ORR was 75%. Of the 4 patients with unmeasurable baseline lesions, 1 was surgically confirmed to achieve pathologic complete response (pCR). The patients had a DCR of 92 percent and a median PFS that had not yet been reached, with an 18-month PFS rate of 73 percent and an 18-month OS rate of 82 percent, as shown in Table 2.
Table 7 Efficacy analysis
The safety analysis showed that no dose-limiting toxicities (DLTs) were observed, and the maximum tolerated dose (MTD) was not reached. Weight loss (33%) and anaemia (33%) were the most common treatment-related adverse events (TRAEs). Two patients (17%) developed grade 3 TRAEs (weight loss and esophageal fistula), and the details of adverse events are shown in Table 3.
Table 8 Security analysis
Pharmacokinetic analysis showed that no interaction was observed with AN0025 in combination with chemoradiotherapy.
Conclusions of the study
The preliminary efficacy of AN0025 combined with chemoradiotherapy in the treatment of locally advanced unresectable esophageal cancer is good and well tolerated, and the investigators suggest that the therapeutic effect of this regimen should be further explored.
Bibliography:
1.Wencheng Z, et al. Iparomlimab and tuvonralimab (QL1706) with definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma: An open-label phase II study. 2024 ESMO 1414P.
2.Liu C, et al. BL-B01D1, an EGFR x her3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). 2024 ESMO 1426P.
3.Nan B, et al. A phase Ib study of AN0025 in combination with definitive chemoradiotherapy (dCRT) in unresectable locally advanced or locally recurrent esophageal cancer (EC). 2024 ESMO 1453P.
Written by: Aurora
Reviewer: Babel
Typography: Aurora
Executive: Babel
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