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Carmen Kahatt



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    P1.12 - Small Cell Lung Cancer/NET (ID 179)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.12-03 - Antitumor Activity of Single Agent Lurbinectedin in Patients with Relapsed SCLC Occurring ≥30 Days After Last Platinum Dose (ID 1710)

      09:45 - 18:00  |  Author(s): Carmen Kahatt

      • Abstract
      • Slides

      Background

      Lurbinectedin (L) inhibits activated transcription and induces DNA double-strand breaks, leading to apoptosis.

      Method

      This multicenter, single agent, phase II Basket trial treated a cohort of 105 SCLC patients (pts) with ECOG PS 0-2 who had received one prior chemotherapy line. L 3.2 mg/m2 was administered as a 1-hour i.v. infusion on Day 1 q3wk. Primary endpoint, confirmed overall response rate (ORR) by RECIST v.1.1 according to investigator assessment, was met (ORR=35.2%; 95% CI, 26.2-45.2%). A sub-analysis excluding the 21 pts with disease relapse < 30 days after last platinum dose is reported here.

      Result

      Median age of 84 evaluated pts was 60 years (range, 41-83), 58.3% were male, ECOG PS 0-1/2 in 96/4%, liver metastasis in 36.9%, history of CNS involvement in 4.8%, prior platinum in 100%, median chemotherapy-free interval (CTFI)=3.9 months (1.1-16.1); prior immunotherapy in 8.3%. A median of 5.5 cycles (range, 1-24) was administered.

      ORR, % (95% CI) (confirmed responses) (n=84)

      40.5 (29.9-51.7)*

      CTFI≥90d (n=60)

      45.0 (32.1-58.4)

      CTFI 30-89d (n=24)

      29.2 (12.6-51.1)

      Disease Control Rate at 6 months, % (n=84)

      48.8

      Median duration of response (months) (95% CI) (n=34)

      5.3 (3.5-6.4)

      CTFI≥90d (n=27)

      6.2 (3.5-7.3)

      CTFI 30-89d (n=7)

      4.1 (2.6-5.3)

      Median overall survival (months) (95% CI) (n=84)**

      10.9 (7.8-14.9)

      CTFI≥90d (n=60)**

      11.9 (9.7-16.2)

      CTFI 30-89d (n=24)**

      (4.1-7.6)

      *4 of 7 pts who failed prior immunotherapy had confirmed response

      **Preliminary data

      L was well tolerated. Neutropenia was the most common adverse event (AE) (G3:21.5% and G4:25%), whereas febrile neutropenia was reported in 2.4%. Most common non-hematological AEs included fatigue (G3: 7.1%), nausea and vomiting (all G1-2: 32.1% and 16.7%) and transaminase increase (G3:7.2%). There was no death due to treatment related AE.

      Conclusion

      L is an active agent for second-line treatment of SCLC. The highest ORR (45.0%) was reported for pts with CTFI≥90d. Notable antitumor activity (ORR=29.2%) was also observed in pts with CTFI 30-89d, for whom no therapy is currently approved. Hence, L is a valuable therapeutic option for SCLC pts with disease relapse after first-line platinum-based therapy.

      Updated trial results will be presented at the conference.

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    P2.12 - Small Cell Lung Cancer/NET (ID 180)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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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 (ID 1588)

      10:15 - 18:15  |  Author(s): Carmen Kahatt

      • Abstract
      • Slides

      Background

      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.

      Method

      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.

      Result

      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%.

      Lurbinectedin-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

      PR

      71% (n=5)

      14% (n=1)

      57% (n=4)

      25% (n=3)

      0%

      25% (n=3)

      ORR in CTFI >90d

      67%

      38%

      CB (CR+PR+SD≥4m)

      71%

      67%

      Median DOR

      2.3 m 95% CI (2.0-NR)

      4.6 m 95% CI (3.0-6.8)

      Median PFS

      4.8 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.

      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).

      Conclusion

      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.

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