1200P - A phase II single-arm interventional trial evaluating the activity and safety of CABOzantinib (CBZ) plus TEMozolomide (TMZ) in lung and gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) progressed after SSA therapy, everolimus, sunitinib or PRRT: CABOTEM Trial

Background

Both CBZ and TMZ have already shown clinical efficacy in patients (pts) with NENs when used in monotherapy. Preclinical evidence demonstrated that downregulation of c-MET increases the sensitivity of glioblastoma cell lines to TMZ, and we hypothesized that CBZ could enhance the clinical efficacy of TMZ against NENs by inhibiting c-MET. The Cabotem trial aims at evaluating the efficacy and safety of CBZ in combination with TMZ as a treatment in lung and GEP-NENs progressive to SSAs, everolimus, sunitinib or PRRT.

Methods

This is a phase II, open-label, single-arm, multicentre study. Thirty-five pts were treated with CBZ (40 mg per os daily continuously) and TMZ 100 mg/m²/day (one week on/one week off). The primary endpoint was overall response rate (ORR) assessed by RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and 1-year OS.

Results

Of the 33 patients enrolled (M: 14, F: 19; pancreas:12; GI: 9; Lung: 8; UNK: 4), 25 are currently evaluable for response. After a median follow-up of 6 months, an ORR of 12% was recorded, with a clinical benefit rate (CR+PR+SD) of 72%. Ten patients prematurely discontinued the treatment (median: 3 months) due to severe adverse events (AEs). The most common G3/G4 treatment-related AEs were thrombocytopenia, palmar/plantar erythrodysesthesia, nausea, vomiting, appetite loss and dysgeusia.

Conclusions

The combination of CBZ and TMZ shows promising antitumor activity in patients with NENs. While tolerability appears to be an issue, the relatively high rate of toxicities observed in this study should be weighted against the characteristics of a heavily pretreated patient population.

Clinical trial identification

EudraCT 2020-001898-78.

Editorial acknowledgement

Legal entity responsible for the study

Istituto Nazionale Tumori IRCCS G. Pascale of Naples.

Funding

Ipsen.

Disclosure

C. von Arx: Financial Interests, Personal, Advisory Board, Receipt of consultation fees, Participation in a company sponsored speaker’s bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Pierre-Fabre, Gentili, Lilly, Novartis, Ipsen; Financial Interests, Personal, Other, Conference Fee and travel grant: Organon; Financial Interests, Personal, Conference fee and travel grant: AAA. All other authors have declared no conflicts of interest.