Lurbinectedin (LUR) in combination with Irinotecan (IRI) in patients (pts) with advanced endometrial carcinoma.

Abstract

5586 Background: LUR is a new agent that exerts antitumor activity through inhibition of trans-activated transcription and modulation of tumor microenvironment. Preclinical synergism/additivity in combination with IRI has been reported, thus prompting the conduct of this trial. This synergism had been evaluated and recently reported in patients with Small Cell Lung Cancer, with encouraging results (Ponce et al. WCLC, 2020). Methods: Phase I trial to evaluate escalating doses of LUR on Day (D) 1 plus a fixed dose of IRI 75 mg/m2 on D1 and D8 every 3 weeks (q3w) in pts with advanced solid tumors, enrolled following a standard 3+3 dose escalation design. Phase II to expand in selected indications at the Recommended Dose (RD). In this abstract, the cohort of patients with endometrial carcinoma treated at the RD is presented. Results: 21 pts (all female) with endometrial carcinoma were treated at the RD (LUR 2 mg/m2 + IRI 75 mg/m2 + G-CSF); 57% had ECOG PS=1; median age was 64 years (range 34-74); subtype of tumour was split: 67% (14 pts) endometroid, 33% non-endometroid (3 pts serous-papilar, 3 pts clear-cell and 1 pt undifferentiated); median of 2 prior lines (range, 1−7) per pt. Common G1/2 toxicities were nausea, vomiting, fatigue, diarrhea and anorexia; G3/4 hematological toxicities comprised neutropenia (33%), thrombocytopenia (5%) and anemia (38%). Two episodes of febrile neutropenia occurred (9.5%). G3/4 non hematological toxicities consisted of diarrhea (24%), asthenia (19%), nausea (14%) and vomiting (5%), all were transient and manageable. 1 patient (5%) discontinued treatment due to toxicity drug-related (generalized muscular weakness), but no treatment-related deaths were reported. Objective RECIST responses were documented in 4/21 evaluable pts (19%). With 6 pts censored for progression, median PFS was 4.4 months (95% CI 2.1-9.6 months), and PFS at 6 months was 40.4%. The clinical benefit rate (% of pts with Complete Response (CR), Partial Response (PR) or Stable Disease > 4 months) was 43%, and the Disease Control Rate (% of pts with CR, PR or SD) 81%. 3/21 pts (14%) have been more than 12 months on treatment so far. Conclusions: The combination of Lurbinectedin and Irinotecan is active in heavily pretreated patients with endometrial carcinoma. The combination was well-tolerated and consistent with the known safety profile for this combination. Myelosuppression, diarrhea, nausea and asthenia were predictable and manageable. Updated results of this cohort will be presented at the meeting. Clinical trial information: NCT02611024.