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P2.12-13 Lurbinectedin (L) Combined with Paclitaxel (P) or Irinotecan (I) in Relapsed SCLC. Results from Two Phase Lb Trials

2019; Elsevier BV; Volume: 14; Issue: 10 Linguagem: Inglês

10.1016/j.jtho.2019.08.1758

1556-1380

Santiago Ponce, Emiliano Calvo, Maria J. de Miguel, C. Sessa, M.J. Flor, A. Drilon, Alejandro Falcón, Ioan Şimon, Ramiro Manzano-Núñez, Xarles Erik Luepke, N. Cuevas-Melendez, José Antonio López-Vilariño, Salvador Fudio, Mariano Siguero, Martín Cullell-Young, Carmen Kahatt, Ali Zeaiter, Luis Paz‐Ares,

Glycosylation and Glycoproteins Research

L is a new agent that exerts antitumor activity through inhibition of trans-activated transcription and modulation of tumor microenvironment. Preclinical evidence of synergism was observed for L in combination with P and I. Activity of combinations with LP and LI in small cell lung cancer (SCLC) was reviewed in two phase Ib trials. Patients were enrolled following a 3+3 dose escalation design. SCLC patients with ECOG performance status (PS) 0-1 and pretreated with at least one platinum-based chemotherapy are presented. Extensive pharmacokinetic (PK) sampling for L and P or I was performed. 19 pts were treated: 7 with LP and 12 with LI. Baseline characteristics (LP/LI) were: males, 57%/45%; median age, 55/57 years; ECOG PS score 1, 57%/92%; chemotherapy-free interval (CTFI) >90 days, 43%/67%; median (range) prior lines, 1 (1-3)/2 (1-3); liver metastases, 29%/33%.Tabled 1Lurbinectedin-Paclitaxel (L: 2.2 mg/m2 – 5 mg FD + P: 60-80 mg/m2) * (n=7)Lurbinectedin-Irinotecan (L: 1-2.4 mg/m2 + I: 75 mg/m2) ** (n=12)ORR (CR+PR) CR PR71% (n=5) 14% (n=1) 57% (n=4)25% (n=3) 0% 25% (n=3)ORR in CTFI >90d67%38%CB (CR+PR+SD≥4m)71%67%Median DOR2.3 m 95% CI (2.0-NR)4.6 m 95% CI (3.0-6.8)Median PFS4.8 m 95% CI (1.8-12.5)5.6 m 95% CI (1.4-8.3)* Combination with P given for up to 6 cycles, followed by single-agent L 2.2 mg/m2. ** One patient received L 3 mg/m2 + I 15 mg/m2. CB, clinical benefit; CR, complete response; CTFI, chemotherapy-free interval; d, days; DOR, duration of response; FD, flat dose; I, irinotecan; L, lurbinectedin; m, months; NR, not reached; ORR, overall response rate; P, paclitaxel; PFS, progression-free survival; PR, partial response; SD, stable disease. Open table in a new tab * Combination with P given for up to 6 cycles, followed by single-agent L 2.2 mg/m2. ** One patient received L 3 mg/m2 + I 15 mg/m2. CB, clinical benefit; CR, complete response; CTFI, chemotherapy-free interval; d, days; DOR, duration of response; FD, flat dose; I, irinotecan; L, lurbinectedin; m, months; NR, not reached; ORR, overall response rate; P, paclitaxel; PFS, progression-free survival; PR, partial response; SD, stable disease. Adverse events (AEs): grade (G) 4 neutropenia LP/LI 43%/27% of patients; no episodes of febrile neutropenia in LI, one (G3) in LP; no G4 anemia or G4 thrombocytopenia in either study. Non-hematological toxicity was mild and mainly consisted of G3 fatigue (18%) and G3 nausea (7%) in LI; no G3/4 toxicities were found in LP. No toxic deaths and no discontinuations were due to AEs. PK: mean clearance of L (12 L/h in combo with P, and 9.5 L/h in combo with I), of P (31.5 L/h) and of I (32.2 L/h) are comparable with reported data (11.2 L/h, 31.4/h and 25 L/h, respectively). LP and LI combinations showed promising activity after first-line therapy in SCLC. This activity seems consistent with that observed in other trials with L given alone or in combination. Both combinations showed acceptable safety profile. So far, no evidence of major PK drug-drug interactions has been observed. Further development of these combinations is warranted.