1261TiP CARMEN-GC01: Phase II, open-label, single-arm study of tusamitamab ravtansine in combination with ramucirumab in pretreated patients with gastric or gastroesophageal junction adenocarcinoma (GA/GEJA)
التفاصيل البيبلوغرافية
العنوان:
1261TiP CARMEN-GC01: Phase II, open-label, single-arm study of tusamitamab ravtansine in combination with ramucirumab in pretreated patients with gastric or gastroesophageal junction adenocarcinoma (GA/GEJA)
Background Tusamitamab ravtansine (tusa; SAR408701), an anti-carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) antibody conjugated to the potent cytotoxic antitubulin DM4, showed promising antitumor activity and was well tolerated in heavily pretreated patients (pts) with advanced non-small cell lung cancer (NSCLC) and high CEACAM5 expression (immunohistochemistry intensity ≥ 2+ in ≥ 50% of tumor cells). High CEACAM5 expression occurs in 30% of pts with gastric cancer (GC). Ramucirumab, an antibody antagonist of vascular endothelial growth factor receptor 2 (VEGFR2), combined with paclitaxel is a standard of care option for second-line (2L) treatment of GA or GEJA. Preclinical studies with tusa and a VEGFR2 antagonist have shown synergistic activity in gastric patient-derived xenografts, supporting clinical investigation of tusa in combination with ramucirumab. This combination may lead to improved 2L outcomes in pts with GC, with a better safety profile compared with that of paclitaxel plus ramucirumab. A phase II study (NCT04394624) of tusa in combination with ramucirumab is also ongoing in pts with NSCLC and high CEACAM5 expression. Trial design CARMEN-GC01 (NCT05071053) is a phase II, open-label, single-arm, multicenter, 2 part study to evaluate tusa combined with ramucirumab in pts pretreated for GA/GEJA with high CEACAM5-expressing tumors. Part 1 is a safety run-in, followed by a Part 2 expansion. Inclusion criteria include age ≥ 18, metastatic or locally advanced GA/GEJA, and ≥ 1 measurable lesion. Key exclusion criteria are untreated brain metastases, unresolved previous corneal disorders, concurrent anticancer therapy, and prior CEACAM5-targeted, DM1- or DM4-containing, anti-VEGF/VEGFR, or taxane treatment. The primary objectives are to confirm the recommended tusa loading dose in combination with ramucirumab (Part 1) and to assess the antitumor activity of tusa (Part 2). Secondary objectives include safety, duration of response, progression-free survival, disease control rate, pharmacokinetics, and immunogenicity. As of April 13, 2022, 22 sites in 6 countries are recruiting.
