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S. Turnbull



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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-017 - Clinical activity of lurbinectedin (PM01183) in combination with gemcitabine (GEM) in non-small cell lung cancer (NSCLC) patients (pts): preliminary subgroup analysis of a phase Ib study. (ID 995)

      09:30 - 09:30  |  Author(s): S. Turnbull

      • Abstract

      Background
      PM01183 is an inhibitor of transactivated transcription and also acts on the tumor microenvironment. It lacks cross-resistance with platinum (Pt) agents. Evidence of synergism with GEM has been observed preclinically. PM01183 is undergoing intensive clinical evaluation as single agent in phase II studies in pancreatic, ovarian, breast and NSCLC pts. Its primary side effects are reversible myelosuppression and high emetogenic potential.

      Methods
      Consenting adults with selected solid tumors (including NSCLC), age ≤ 75 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, adequate major organ function and up to 2 prior chemotherapy-containing (CT) lines were included in successive cohorts aiming to primarily define the recommended dose (RD) of PM01183 when combined with GEM, both on Days 1 and 8 every three weeks (q3wk). Prior GEM was not allowed in the metastatic setting. Available results exclusively from the NSCLC population are described here.

      Results
      Recruitment was closed in December 2012. Overall, 22 of 45 treated pts (49%) had NSCLC. Of these, 73% were males. Median age was 65 years (r: 37-73). Patients received 1, 2 or 3 prior lines, in 64/27/9% of cases respectively. Non-squamous histology was reported in 91% of pts and 18% had known central nervous system (CNS) involvement. Five of 14 pts evaluable for efficacy by Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1, responded to therapy [4 PRs and 1 CR], reaching an overall response rate (ORR) of 36% [95% confidence interval (CI): 13-65] in the RECIST evaluable population. Median response duration was 31 weeks (r: 7-52+). Eight of 22 pts were not evaluated for efficacy, as this was not the primary endpoint of the phase Ib study. Nevertheless, on an intention-to treat basis the ORR was 23% (95%CI: 8-45). Severe myelosuppression, G3/4 neutropenia or thrombocytopenia, was observed in 67/42% of pts, respectively. Other toxicities, in ≥ 10% of pts, were generally mild and comprised anemia, ALT/AST or creatinine increases, fatigue, mucositis, nausea/vomiting and anorexia. No alopecia was reported. Serious adverse events included febrile neutropenia (FN), pneumonia, sepsis and shock, and resulted in two treatment-related deaths, both occurred at dose levels over the RD. The RD was established at PM01183 3.0 mg + GEM 800 mg/m[2] on Days 1 and 8 q3wk.

      Conclusion
      PM01183 and GEM combination resulted in relevant and durable clinical activity in NSCLC pts. Toxicity seems both manageable and predictable at the RD. The novel mechanism of action of PM01183, and particularly its lack of Pt cross-resistance are of special interest in this population. A randomized trial is ongoing to assess the role of this new CT combination in relapsed NSCLC.

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    P1.13 - Poster Session 1 - SCLC (ID 200)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.13-001 - Clinical activity of lurbinectedin (PM01183) in combination with doxorubicin (DOX) in small cell lung cancer (SCLC) patients (pts): preliminary results of a phase Ib study subpopulation analysis. (ID 954)

      09:30 - 09:30  |  Author(s): S. Turnbull

      • Abstract

      Background
      PM01183 is an inhibitor of transactivated transcription and also acts on the tumor microenvironment. It lacks cross-resistance with platinum (Pt) agents whereas strong synergism with DOX has been observed preclinically. Single agent PM01183 clinical evaluation in non-small cell lung cancer (NSCLC), pancreatic, ovarian and breast cancer patients (pts) is ongoing. Reversible myelosuppression and high emetogenic potential are common side effects.

      Methods
      Consenting adults with selected solid tumors, including SCLC, and ≤ 75 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, adequate organ function and up to 2 prior chemotherapy-containing (CT) lines were included in successive cohorts aiming to primarily define the recommended dose (RD) of PM01183 and DOX (50 mg/m[2], fixed dose) combination every three weeks (q3wk). No prior DOX was allowed in the metastatic setting. DOX had to be discontinued once a maximal cumulative dose of 450 mg/m[2] during treatment was reached. Available results in the SCLC population are presented here.

      Results
      Recruitment was closed in December 2012; 13 of 43 enrolled/treated pts (30%) had SCLC diagnosis. Of these, 8 (62%) were males. Median age was 58 years (r: 48-73). Ten (77%) and 2 pts (15%) were chemo-refractory or had known central nervous system (CNS) involvement, respectively. Five of 12 pts evaluable for efficacy [Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1] were responders, for an overall response rate (ORR) of 42% [95% confidence interval (CI): 15-72]. No responses occurred in pts with >1 prior CT lines (n=5). In evaluable pts with 1 prior CT line (n=7), the ORR reached 71% (95%CI: 29-96). All chemosensitive pts (n=3) responded to treatment. Severe myelosuppression, G3/4 neutropenia or thrombocytopenia, was observed in 89/22% of pts, respectively. Other toxicities, in ≥ 10% of pts, were generally mild and included transaminase increases, fatigue, alopecia, mucositis, nausea/vomiting, diarrhea, anorexia and constipation. No cardiac toxicity was observed. Febrile neutropenia (FN) occurred in 11% of pts. Overall, 2 pts discontinued treatment due to toxicity (pneumonia; and repetitive myelosuppression despite successive dose adjustments, respectively). No treatment-related deaths occurred. The RD was defined as PM01183 4.0 mg and DOX 50 mg/m[2] q3wk.

      Conclusion
      PM01183 and DOX resulted in relevant activity in SCLC patients with less than 2 prior CT-lines. Toxicity with this combination seems both manageable and predictable. Despite the high level of myelosuppression, FN was relatively uncommon and colony-stimulating factors (CSFs) are not currently indicated. The novel mechanism of action, and particularly the lack of Pt cross-resistance, is of interest in this patient population. These results warrant further study of the potential role of this regimen in relapsed SCLC pts.