Osemitamab plus CAPOX proven safe, prolongs survival in advanced G/GEJ cancer

First-line treatment with TST001 (osemitamab) in combination with capecitabine and oxaliplatin (CAPOX) is safe and well tolerated in patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer, according to a study presented at ESMO 2023.

“The addition of TST001 to CAPOX as first-line treatment in patients with CLDN18.2-expressing G/GEJ cancer leads to encouraging and durable antitumour activities with longer duration of response (DoR) and progression-free survival (PFS) as compared to historical controls,” said the researchers, led by Lin Shen from Peking University Cancer Hospital in China.

Shen and colleagues conducted the Transtar102-Cohort C study to explore the safety and efficacy of CAPOX plus osemitamab as first-line treatment in advanced G/GEJ cancer.

Positive CLDN18.2 expression, characterized by membranous staining intensity ≥1+ in ≥10 percent of tumour cells using IHC 14G11 LDT assay, was necessary in the dose expansion phase and retrospectively conducted in dose escalation and safety run-in phase. Participants with CLDN18.2 expression comprised nearly 55 percent of all G/GEJ cancer patients.

Sixty-four patients received CAPOX plus osemitamab as of 7 September 2023. Of these, 15 received osemitamab 1 to 8 mg/kg Q3W in the dose escalation phase, and 49 received 6 mg/kg in the dose expansion phase. The median follow-up for the 49 patients was 11.3 months, with the longest treatment duration being 1.5 years. The Transtar102-Cohort C study is still in progress.

Forty-one patients in the dose expansion phase presented with CLDN18.2 positive tumour (high: n=9; medium: n=13; low: n=19 per CLDN18.2 expression levels), while the remaining eight patients did not undergo biomarker testing (unknown CLDN18.2 expression). [ESMO 2023, abstract 1524P]

Baseline demographics of the 49 patients were comparable to the overall participants in this cohort. Most of the patients (81.6 percent) had ECOG performance status 1, while 34.7 percent had three or more metastatic lesions. [J Clin Oncol 2023;41(suppl 16):4046]

Peritoneum metastasis, a significant predictor of poor prognosis, was found in 25 patients (51 percent), while 10 (20.4 percent) and eight (16.3 percent) had hepatic and pulmonary metastases, respectively.

The 49 patients in the dose expansion phase showed a similar profile to that of the overall population in this study. Adverse events (AEs) were characterized by manageable on-target-off-tumour effects, such as nausea, hypoalbuminaemia, and vomiting. Most AEs were grade 1 or 2 and occurred during the first two cycles. [J Clin Oncol 2023;41(suppl 16):4046]

During the cutoff date, 28 of the 42 patients who had measurable lesions at baseline and at least one postbaseline tumour assessment achieved partial response. Of these, 23 (54.8 percent) had been confirmed. The 23 responders had a median DoR of 12.7 months. Additionally, 20 of the 49 patients experienced disease progression or died. Their estimated median PFS was 14 months.

“The overall survival data is immature and requires further follow-up,” the researchers said.

Osemitamab is a “potential best-in-class antibody with improved CLDN18.2 affinity and enhanced ADCC (antibody-dependent cell-mediated cytotoxicity) effect, leading to antitumour activity in low to medium CLDN18.2 expression gastric cancer animal models,” according to the researchers.