Pharmamar con fecha 4 de junio de 2018 ha suscrito un contrato de liquidez con la entidad JB Capital Markets, Sociedad de Valores, S.A.U. con el objeto de favorecer la liquidez de las transacciones y la regularidad de la cotización de sus acciones.

Aplidin ( Plitidepsin ) ASCO18 - 4 de Junio . Aplidin en Combinación con DXM Demostró un Beneficio Clínicamente Significativo en Términos de Supervivencia Global en RRMM Altamente Pretratados . Una Enfermedad donde todavía se Necesitan Nuevas Alternativas Terapéuticas.

Overall Survival (OS) Results of Randomized Phase III study (ADMYRE trial) of Plitidepsin and Dexamethasone (DXM) vs. DXM Alone in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) : 

Evaluation of the Crossover Impact.

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Meeting : 2018 ASCO Annual Meeting

Author(s) : Javier Gomez, Sonia Extremera, Antonio Nieto; PharmaMar, Madrid, Spain.

Abstract:

Background: 

Plitidepsin is a synthetic cyclic depsipeptide isolated from the marine tunicate Aplidium albicans targeting the proto-oncogene eEF1A2, which is over-expressed in multiple myeloma cells. In ADMYRE trial, Plitidepsin plus dexamethasone (DXM) (Arm A) met the primary endpoint (progression-free survival) and showed a survival improvement versus DXM alone (Arm B) (ASH 2017).

Methods: 

RRMM patients with at least three but not more than six prior regimens, including at least bortezomib and lenalidomide/thalidomide, were randomized at 2:1 ratio to receive plitidepsin 5 mg/m2 D1 and 15 plus DXM 40 mg D1,8,15 and 22 (Arm A), or DXM 40 mg D1,8,15 and 22 (Arm B) every four weeks. The rank preserving structural failure time (RPSFT) and the two-stage methods were used to present overall survival (OS) results after mitigating the crossover effect.

Results:

Two-hundred fifty-five patients were enrolled: (Arm A: 171/Arm B: 84). Thirty-seven patients in Arm B (44%) switched to Arm A after progression. Intention-to-treat (ITT) analysis not discounting the crossover effect showed a 20.3% risk reduction in favor of Arm A (median OS: A 11.6 mo. B: 8.9 mo.; HR = 0.797; log-rank p = 0.1261). Risk reduction improved to 32.4% with the RPSFT method (median OS: A 11.6 mo. B: 7.2 mo.; HR = 0.676; log-rank p = 0.0103) and to 37.8% with the two-stage method (median OS: A 11.6 mo. B: 6.4 mo.; HR = 0.622; log-rank p = 0.0015). Although assumptions for RPFST and two-stage analyses were plausibly met, statistically significant risk reductions were still maintained when severe penalizations were applied, with median OS differences around four months.

Conclusions: 

Plitidepsin in combination with DXM demonstrated a clinically significant benefit in terms of overall survival in heavily pretreated RRMM, a disease where new therapeutic alternatives are still needed.

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Zepsyre ASCO18 - 4 de Junio . Fase 1 en Pacientes Japóneses .

Phase I Trial of Lurbinectedin (PM1183) in Japanese Patients with Advanced Tumors: Results of the Dose Escalation Part.

Presented Monday, June 4, 2018


Authors:

Shunji Takahashi, Toshio Shimizu, Toshihiko Doi, Jose Antonio Lopez-Vilariño, Rafael Nuñez, Carmen Maria Kahatt, Carlos Fernandez, Katrin Zaragoza, Hiromi Sasamoto, Arturo Soto-Matos; Cancer Institute Hospital of JFCR, Tokyo, Japan; Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan; National Cancer Center Hospital, Chiba, Japan; PharmaMar, Madrid,... View More

Abstract Disclosures

Background:

PM1183 (lurbinectedin, Zepsyre) is a new anticancer agent that inhibits activated transcription, induces DNA double-strand breaks leading to apoptosis and modulates tumor microenvironment. The recommended dose (RD) in non-Japanese patients (pts) is 3.2 mg/m2 on Day 1 every three weeks (q3wk), with reversible myelosuppression as dose-limiting toxicity (DLT).


Methods:

Japanese pts with solid tumors (excluding CRC or CNS primary tumors), adequate organ function and ECOG PS 0-2 were treated at 3 different dose levels (DLs), 1.5 mg/m2, 2.5 mg/m2 and 3.2 mg/m2, using a 3+3 design.

Results:

Fifteen pts (10 female / 5 male) were treated and evaluated for safety and efficacy. Median age was 52 years (38-65), albumin 4 mg/dL (3.5-4.6) with 2 median previous lines (1-3). Tumors were, among others, biliopancreatic (3), esophageal (2), endometrial (2) and breast (1). 2 out of 4 pts on DL3 (3.2 mg/m2) had a DLT consisting of a grade (G) 4 neutropenia and a G3 neutropenia lasting > 7 days. Eight pts were treated at the RD established on 2.5 mg/m2, with G2 neutropenia leading to dose reduction and dose delay in 1 pt each. Main adverse events at the RD were hematological with 1 pt (12.5%) presenting G3 neutropenia. Other G3/4 toxicities included a non-drug related G4 hypokalemia (12.5%). Non-hematological toxicities were exclusively G1/2, including G2 ALT increase (50%), AST increase (25%), anorexia (25%), nausea (25%), fatigue (12.5%) and dyspnea (12.5%). At RD, 1 pt (12.5%) with metastatic breast cancer achieved a durable partial response and 3 pts (37.5%) had confirmed stable disease. PK at RD (n= 6 pts) showed a similar behavior to non-Japanese pts, with a mean (standard deviation) total body clearance (CL) of 10.5 (4.5) L/h, half-life of 50.7 (18.1) h and volume of distribution at steady-state of 375.5 (172.0) L.

Conclusions:

The RD of PM1183 in Japanese pts is 2.5 mg/m2 q3wk, with mild toxicity. Main DLTs were hematological. Hints of activity were observed in breast cancer. Japanese pts showed a similar CL to non-Japanese pts, but with a 26.5% lower distribution volume. A new cohort is exploring PM1183 3.2 mg/m2 (non-Japanese RD) in Japanese pts receiving G-CSF support.

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Yondelis ASCO18 - 4 de Junio . A French Sarcoma Group (FSG) Trial.

Results of a Prospective Randomized Phase III T-SAR Trial Comparing Trabectedin (T) vs Best Supportive Care (BSC) in Patients with Padvanced Soft Tissue Sarcoma (ASTS): A French Sarcoma Group (FSG) Trial.

Presented Monday, June 4, 2018 .

Authors:

Axel Le Cesne, Jean-Yves Blay, Didier Cupissol, Antoine Italiano, Corinne Delcambre, Nicolas Penel, Nicolas Isambert, Christine Chevreau, Emmanuelle Bompas, Francois Bertucci, Loic Chaigneau, Sophie Piperno-Neumann, Sébastien Salas, Maria Rios, Cecile Guillemet, Jacques Olivier Bay, Isabelle Laure Ray-Coquard, Leila Haddag, Olivier Mir, Stéphanie Foulon; Gustave Roussy Cancer Campus,... View More

Abstract Disclosures

Background:

With the exception of a study in translocation-related STS (Kawai, 2015), T has never been compared to BSC in a study including patients (pts) with all sarcoma histotypes. The efficacy, safety and quality of life of T vs BSC as second or later treatment line were evaluated in pts with ASTS in a multicenter FSG trial.

Methods:

The study enrolled pts ≥18 years of age with histologically proven ASTS who progressed after at least 1 anthracycline-containing regimen (≤3 previous chemotherapy (CT) lines), stratified by L-STS (lipo-leiomyosarcoma) and non L-STS and with a WHO performance status score 0-1. Pts were randomized 1:1 to receive either T (1.5 mg/m2 24h every 3 weeks) or BSC until disease progression (PD), unacceptable toxicity, or patient’s request. Pts allocated to BSC could cross over to T at PD. The primary endpoint was progression-free survival (PFS).

Results:

Between January to November 2015, 103 pts (median 65 yrs (range 22-84), grade 3 ASTS in 57% of cases, median number of 1 prior CT lines) were enrolled by 16 FSG centers, 52 in the T arm and 51 the BSC arm. Pts with L-STS and non L-STS represented 60% and 40% of pts, respectively. Two pts refused to be allocated in the BSC arm and received other CT. The objective response rate (ORR) in the T arm was 11.8%, all observed in the L-STS group (ORR: 18.8% in L-STS). 23% of pts in the T arm received more than 9 cycles of T. The median PFS were 1.5 months (m) in the BSC arm and 3.1m in the T arm (HR: 0.39, p < 0.0001). In the L-STS cohort, the median PFS were 1.4m and 5.1m in the BSC and T arm (HR: 0.29, p < 0.0001), respectively, whereas in the non L-STS group they were 1.5m and1.8 m (p = 0.16). A cross-over was performed in 92% of pts included in the BSC arm. By After a median follow-up of 25.7 months, the differences on OS were not statistically significant between the two arms, 13.6 m vs 10.8 m in the T and BSC arms respectively (p = 0.86).

 Conclusions: 

This study met its first endpoint as a preplanned PFS analysis showed a significant improvement in median PFS with T over BSC in pts with pretreated ASTS of multiple histologies. L-STS pts benefit the most from T therapy in terms of prolonged tumor control.

Zepsyre . Tumori: la ricerca vien dal mare, caccia a nuove armi contro il cancro dei bimbi .

 Filomena Fotia

Il sarcoma di Ewing – tumore raro che colpisce soprattutto bambini e adolescenti under 20 – passa inizialmente inosservato, anche allo sguardo attento di mamma e papà. I suoi sintomi si possono confondere con i postumi di una caduta, ma quando dolore e infiammazione non guariscono in tempi ragionevoli devono scattare un’analisi approfondita e indagini più mirate. Ed è allora che arriva la diagnosi, una fitta al cuore che sperimentano le famiglie di un centinaio di pazienti ogni anno.

Il Sarcoma di Ewing rappresenta il 15% di tutti i sarcomi primari delle ossa: il dolore è il sintomo principale e come altri è molto aspecifico (febbre, stanchezza o perdita di peso). Talvolta il tumore può disseminato in altri organi lontani e, in caso di micrometastasi, anche in maniera così piccola da risultare invisibile agli esami.

Dal mare arriva l’ispirazione alla ricerca che sta esplorando una potenziale arma per combattere questa neoplasia. Si chiama lurbinectedina e mima molti composti naturali di origine marina. I dati di uno studio sperimentale internazionale su questo nuovo agente terapeutico (Pm1183) che blocca la trascrizione e induce rotture del doppio filamento del Dna, portando alla morte della cellula malata, sono stati presentati al Congresso degli oncologi americani dell’Asco (American Society of Clinical oncology). La ricerca ha coinvolto un centro italiano, l’Istituto ortopedico Rizzoli di Bologna, con l’Università del Texas, l’Anderson Cancer Center di Houston in Texas, il Sarcoma Oncology Center di Santa Monica in California, l’Università del Colorado a Denver, l’Hospital Vall D’Hebron di Barcellona, l’ospedale universitario Sanchinarro di Madrid e l’Istituto Jules Bordet di Bruxelles.

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Zepsyre . Una nuova molecola aumenta la sopravvivenza dei pazienti con il raro sarcoma di Ewing .

redazione 3 Giugno 2018 .

È un tumore raro che colpisce soprattutto bambini e adolescenti. Rappresenta il 15% di tutti i sarcomi primari delle ossa e il suo sintomo principale è il dolore.

Ora per il sarcoma di Edwin dal congresso annuale dell’arriva una nuova opzione terapeutica: il farmaco lurbinectedina (PM1183) che in uno studio di fase II ha mostrato la capacità di stabilizzare la terapia. 

La sperimentazione ha coinvolto 28 pazienti con un’età media di 33 anni. È stato condotto all’Istituto Ortopedico Rizzoli di Bologna con l’Università del Texas, l’Anderson Cancer Center di Huston in Texas, il Sacroma Oncology Center di Santa Monica in California, l’Università del Colorado a Denver, l’Hospital Vall D’ Hebron di Barcellona, L’Ospedale universitario Sanchinarro di Madrid e l’Istituto Jules Bordet di Bruxelles. 

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Zepsyre . I ‘piccoli eroi’ correranno contro il sarcoma di Ewing .

3 GIUGNO, 2018 .

A fine giugno ci sarà una corsa non competitiva di bambini (e non solo) vestiti da supereroi con la ‘Super Hero Run’ e il ricavato andrà ad un’associazione pazienti sul sarcoma di Ewing

Si contano appena un centinaio di casi ogni anno ma la diagnosi è per ogni genitore una fitta al cuore. Il sarcoma di Ewing è un tumore raro ma colpisce soprattutto bambini e adolescenti under 20 e rappresenta il 15 per cento di tutti i sarcomi primari delle ossa. Il dolore è il sintomo principale e come altri è molto aspecifico (febbre, stanchezza o perdita di peso) e a volte si confonde con cause totalmente indipendenti da un tumore come una caduta. Ma se il dolore e l'infiammazione non guariscono in un tempo ragionevole, è però opportuno rivolgersi al medico, per un’analisi approfondita e indagini più mirate. A volte infatti può anche esser disseminato in altri organi lontani e, in caso di micrometastasi, anche in maniera così piccola da risultare invisibile agli esami. Di questa tremenda malattia si parla al congresso americano di oncologia (Asco) di Chicago, che riunisce fino al 5 giugno quasi 40 mila persone tra specialisti, associazioni, caregiver provenienti da tutto il mondo. In particolare verrà presentato uno studio sulla lurbinectedina (PM1183), un nuovo agente terapeutico contro il sarcoma di Ewing, che blocca la trascrizione e induce rotture del doppio filamento del Dna, portando alla morte della cellula malata.

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Zepsyre ASCO18 - 3 de Junio . Resultados de la Fase II con " Lurbinectedin como Agente Único " para el Tratamiento de Pacientes con Cáncer de Pulmón de Celulas Pequeñas ( SCLC ) . " Compelling Activity ".

Madrid , 4 de Junio 2018 . 

PharmaMar presenta nuevos resultados con lurbinectedina como agente único en pacientes con cáncer de pulmón microcítico recurrente en ASCO 2018 .

• Se trata del ensayo basket de fase II que comenzó reclutando 15 pacientes con cáncer de pulmón microcítico recurrente y que se ha  ampliado a 100, tras obtenerse respuestas positivas.
   
• En un total de 61 pacientes ya analizados, se han observado respuestas en un 39,3%, con una mediana de duración de respuesta de 6,2 meses, y una mediana de supervivencia global de 12 meses. 

• El objetivo principal del estudio es la tasa global de respuesta, con  otros objetivos secundarios que incluyen la duración de respuesta, la supervivencia libre de progresión, la supervivencia global y el perfil de seguridad.

• “Los pacientes incluidos en este estudio con cáncer de pulmón microcítico están respondiendo favorablemente al tratamiento con lurbinectedina como agente único. Hemos observado que la molécula es activa en este grupo de pacientes, sin embargo tendremos más información una vez terminemos el reclutamiento y evaluemos a todos los pacientes”, explica el Dr. Arturo Soto, director del departamento de Clínica de la unidad de negocio de Oncología de PharmaMar.

Efficacy and Safety of Lurbinectedin (PM1183) in Small Cell Lung Cancer (SCLC) : Results from a Phase 2 Study.

Sub-category : Small Cell Lung Cancer

Abstract No : 8570

Author(s) : Jose Manuel Trigo Perez, Alexandra Leary, Benjamin Besse, Daniel E. Castellano, Santiago Ponce Aix, Jennifer ARRONDEAU, Victor Moreno, Bernard Doger, Rafael Lopez, Ahmad Awada, Christiane Jungels, Martin David Forster, Valentina Boni, Pilar Lardelli, Mariano Siguero, Carmen Maria Kahatt, Arturo Soto-Matos, Rebecca Sophie Kristeleit; Hospital Virgen de la Victoria, Malaga, Spain; Gustave Roussy Cancer Campus, Villejuif, France; Gustave Roussy, Villejuif, France; Hospital 12 de Octubre, Madrid, Spain; Hôpital Cochin, Paris, France; START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain; IDIS; CIBERONC,Hospital Clínico Universitario de Santiago de Compostela, Santiago De Compostela, Spain; Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; University College London Hospitals, London, United Kingdom; START Madrid-CIOCC, Hospital Universitario San Chinarro, Madrid, Spain; PharmaMar, Madrid, Spain


Abstract Disclosures

Abstract :

Background : SCLC is a deadly cancer and despite initial 80% response, almost all patients (pts) will relapse and die of this disease. Limited options exist after failure of first line, with a median time to progression (TTP) of around 3.5 months. New therapeutic agents are needed. Lurbinectedin (L) is a new anticancer drug that blocks transcription and induces DNA double-strand breaks, leading to apoptosis.

Methods : A multicenter phase 2 basket trial to assess the efficacy and safety of L in several types of advanced solid tumors, including SCLC, is ongoing. In the SCLC cohort, 15 adult patients without brain metastases, who had received one prior chemotherapy line, were recruited. If at least one confirmed response was observed, recruitment would be increased to 100 patients. The study intervention comprised L 3.2 mg/m2 in a 1-hour infusion every 3 weeks.

Results : 50 pts were treated and evaluable for efficacy. Median age was 60 years (range, 40-83) and 29 (58%) were males. 45 (80%) had an ECOG of 0/1. 34 pts (68%) had metastatic disease at study entry. 25 (50%) pts had a chemotherapy free interval (CTFI) ≥ 90 days and 22 (44%) had a CTFI < 90 days (unknown in 3). Pts received a median of 5 cycles of therapy (range, 1-18) and a median total dose of 15.9 mg/m2 (range, 2.9-58.2). Nineteen pts (38%) had a partial response (PR); among pts with CTFI ≥ 90 days, 52% (13/25) had a PR. Twenty pts (40%) had disease stabilization, 6 of them for > 4 months. Median response duration was (K-M) 5.3 (CI 95% 2.8-8.8) and median progression free survival (PFS) was 4.2 months (CI 95% 2.8-6.3). Median PFS for pts with CTFI ≥ 90 days was 4.7 months 95% CI (3.1-7.4). Myelosuppression was the most common adverse event: 44% neutropenia grade (G) 3/4, 12% febrile neutropenia, and 8% thrombocytopenia G 3/4; 8 pts had dose delay due to neutropenia G2-4, and 10 pts had dose reduced because of neutropenia G4. G-CSF was given to 9 pts. There was one protocol-defined withdrawal due to neutropenia.

Conclusions : Lurbinectedin as a single agent shows compelling activity as second line treatment in SCLC, with an acceptable tolerability and manageable safety profile. No unexpected or grade 5 toxicity occurred. Updated results will be presented. 

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