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Zalypsis is provided as a lyophilized powder for concentrate for solution for infusion in a strength of 2.5 mg/vial.

Zalypsis

Fariba Navid, MD

Sant P Chawla, MD

Jean Yves Blay, MD

Stefano Ferrari, MD

Armando Santoro, Prof.

Paolo Casali, MD

Robin L. Jones, MD

This is a phase II Multicenter, Open-label, Clinical and Pharmacokinetic Study of Zalypsis® (PM00104) in Patients with Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy to determine the antitumor activity of Zalypsis.

Study of Zalypsis® (PM00104) in Patients With Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy

Phase II Multicenter, Open-label, Clinical and Pharmacokinetic Study of Zalypsis® (PM00104) in Patients With Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy

Overall response rate (ORR), defined as the percentage of patients with confirmed objective response (OR), either CR or PR according to the RECIST v.1.1.

CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; RECIST, Response Evaluation Criteria in Solid Tumors

Best tumor response was defined as the best response achieved during the study according to RECIST v1.1 CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; RECIST, Response Evaluation Criteria in Solid Tumors

Progression-free survival (PFS), defined as the time from the first day of study treatment to the day of negative assessment (progression or death), start of subsequent antitumor therapy, or last tumor evaluation.

PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density

Overall survival (OS), defined as the time from the first day of treatment to the date of death (or the last day when the patient was known to be alive). Survival was to be followed for up to six months after the last treatment visit of the last patient, or 12 months after the last patient was included, whichever occurred first.

Cmax Maximum plasma concentration, directly determined from the experimental data

AUC Area under the plasma concentration-time curve from time zero to infinity

PharmaMar

Sixteen of 17 patients included in this study were treated with PM00104 and were therefore evaluable for safety

PM00104 was administered at a dose of 2 mg/m2 as a 1-hour i.v. infusion d1, d8 and d15 q4wk to patients with advanced and/or metastatic Ewing's sarcoma previously treated with at least one line of chemotherapy. A treatment cycle consisted of PM00104 administration on Days 1, 8 and 15, plus one week of follow-up. Study evaluations had to be completed during each cycle prior to subsequent PM00104 infusion. Treatment cycles were repeated every four weeks

PM00104

Age, Categorical

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Italy

France

Region of Enrollment

Eastern Cooperative Oncology Group Performance Status, ECOG PS 0 Fully active, able to carry on all pre-disease performance without restriction

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
2. Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
3. Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4. Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5. Dead

ECOG PS

Tumor diagnosis

Primary location at diagnosis

Metastatic disease

Time from diagnosis to first infusion

Time from last disease progression to first infusion

Sites of disease at diagnosis

Prior radiotherapy

Prior Antitumor surgery (palliative or curative)

Prior Systemic anticancer therapy

Clinical Developtment, Department of PharmaMar´s Oncology., Business Unit.

Overall Response Rate (ORR)

One patient never treated Two patients were non-evaluable for efficacy because they were withdrawn due to toxicity without any tumor assessment after the start of study treatment and were considered as "treatment failures"

Best Tumor Response

Progression-free Survival

Progression-free Survival at 3 Months

Overall Survival

Overall Survival Rate at 6 Months

Overall Survival Rate at 12 Months

Fourteen of the 16 patients treated in this study had plasma profiles

PM00104 Plasma PK Parameters (Cmax) at First Infusion

PM00104 Plasma PK Parameters (AUC) at First Infusion

Eleven of the 16 patients treated in this study had plasma profiles at second infusion

PM00104 Plasma PK Parameters (Cmax) at Second Infusion

PM00104 Plasma PK Parameters (AUC) at Second Infusion

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Zalypsis® (PM00104) in Patients With Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy	NCT01222767	Ewing's Sarcoma Primitive Neuro... Askin's Tumor o... Extraosseous Ew...	Zalypsis	16 Years -	PharmaMar
Study of Zalypsis® (PM00104) in Patients With Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy	NCT01222767	Ewing's Sarcoma Primitive Neuro... Askin's Tumor o... Extraosseous Ew...	Zalypsis	16 Years -	PharmaMar

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