Lauren Dembeck, PhD

GI Oncology Now

The Claudin18.2 (CLDN18.2) antibody-drug conjugate IBI343 is well tolerated and continues to show encouraging efficacy in patients with pancreatic ductal adenocarcinoma (PDAC), according to <a href="https://meetings.asco.org/abstracts-presentations/246304" target="_blank" rel="noopener">results from a phase I dose expansion cohort</a> to be presented at the 2025 American Society for Clinical Oncology Annual Meeting.&ldquo;CLDN18.2 is highly expressed in nearly 60% of PDAC cases. Yet to date, there are no approved targeted therapies and prognoses for these patients remain poor,&rdquo; explained the study investigators. &ldquo;IBI343, consisting of an anti-CLDN18.2 Fc silenced monoclonal antibody and the topoisomerase I inhibitor, exatecan, is the first CLDN18.2 antibody-drug conjugate to have shown encouraging efficacy in PDAC.&rdquo;The investigators report results from a phase 1 study (ClinicalTrials.gov ID: <a href="https://clinicaltrials.gov/study/NCT05458219" target="_blank" rel="noopener">NCT05458219</a>) in patients with PDAC treated with IBI343, with findings stratified by CLDN18.2 expression status (positive, defined as CLDN18.2 expression of immunohistochemistry staining intensity &ge;1 in &ge;60% of tumor cells, vs negative, &lt;60% of tumor cells).The study enrolled eligible patients with advanced PDAC and moderate to high expression of CLDN18.2 who failed or were intolerant to standard treatment. Participants received IBI343 every 3 weeks at multiple dose levels (1, 3, 4.5, 6, 8, and 10 mg/kg). Study endpoints include safety, objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) per RECIST v1.1, and overall survival (OS).As of December 27, 2024, the study enrolled a total of 83 patients. Of those, 44 patients with CLDN18.2-positive status and 12 patients with CLDN18.2-negative status received IBI343 at 6 mg/kg in the dose expansion phase. Among these CLDN18.2-positive and -negative groups, the median age was 60 and 64 years; 54.5% and 66.7% of patients were male; and 61.4% and 83.3% of patients received greater than or equal to two lines of prior treatment, respectively.Among patients treated at all dose levels (n = 83), 98.8% of patients experienced treatment-emergent adverse events (TEAEs), with greater than or equal to Grade 3 (G3) TEAEs reported in 50.6% of patients. The most common TEAEs were anemia (66.3%; &ge;G3, 15.7%), decreased neutrophil count (48.2%; &ge;G3, 9.6%), and decreased WBC count (47.0%; &ge;G3, 9.6%). TEAEs led to treatment discontinuation in 7.2% of patients. No TEAE resulted in death.Among patients treated at the 6 mg/kg dose level, those with CLDN18.2-positive status (n = 44) had a confirmed ORR of 22.7% (95% confidence [CI], 11.5-37.8%), DCR of 81.8% (95% CI, 67.3-91.8%), median PFS of 5.4 months (95% CI, 4.1-7.4 months), and median OS of 8.5 months (95% CI, 6.6-12.1 months). Additionally, among patients with confirmed partial response (n = 10), the median DOR was 6.7 months (95% CI, 3.2-7.7 months). Among patients with CLDN18.2-positive status who received one and two lines of prior treatment, the median OS was 12.1 (95% CI, 6.6-not calculable [NC]) months and 9.1 (95% CI, 5.1-NC) months, respectively.Patients with CLDN18.2-positive status (n = 12) had no objective responses, DCR of 41.7% (95% CI, 15.2-72.3), median PFS of 1.4 months (95% CI, 1.3-3.2 months; vs 5.4 months in CLDN18.2-positive group; P &lt;.0001; hazard ratio, 0.198; 95% CI, 0.089-0.439) and median OS of 6.2 months (95% CI,1.4-9.0 months).&ldquo;IBI343 was well tolerated and continues to show encouraging efficacy in [patients] with PDAC,&rdquo; concluded the investigators. &ldquo;Efficacy benefit was most pronounced in those with CLDN18.2 expression &ge;60%, suggesting that CLDN18.2 can be a predictive biomarker for response to IBI343 in PDAC.&rdquo;The trial is currently enrolling patients in Australia, China, and the U.S.Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors&rsquo; disclosures.

Adjuvant Nivolumab Gives Long-Term DFS Benefit in EC/GEJC

Esophageal Cancer

10-Year KEYNOTE-016: Pembrolizumab Durable in MSI-H/dMMR Tumors

Colorectal Cancer

Emily Menendez

Chemoradiation Plus Chemotherapy Can Improve OS, Resection Rates for Gallbladder Cancer: The Phase 3 POLCAGB Study

Liver Cancer

Latest News

Claudin18.2-Targeted ADC Shows Safety and Efficacy in PDAC

Pancreatic Cancer

The Claudin18.2 antibody-drug conjugate IBI343 is well tolerated and shows encouraging efficacy in patients with PDAC.