(By JALO).- WCLC 2016 // December 7 .-ANNA FARAGO, MD, PhD Massachusetts General Hospital will be at poster session Presenting the ATLANTIS Clinical Trial on 2nd Line SCLC with PhrmMar PM01183 .
Background:
PM01183 (lurbinectedin) is a new anticancer drug that blocks trans-activated transcription, induces DNA double-strand breaks and modulates the tumor microenvironment. Synergism in combination with doxorubicin with compelling overall response rates (~67%, including approximately 10% complete responses) was reported in a phase I expansion cohort in 21 second-line SCLC patients (pts) (ASCO 2015, abstract 7509). The most common toxicity observed was hematologic.
Methods:
Multinational, multicenter (>150 sites), open-label, randomized, phase III study of PM01183/doxorubicin vs. a control arm with investigator choice of either standard CAV or topotecan (1.5 mg/m[2], D1-5 q3wk).
A total of 600 pts will be randomized (1:1) and stratified according to ECOG performance status (PS), chemotherapy-free interval (CTFI), known CNS involvement, prior PD-1/PD-L1 based immunotherapy and potential investigator’s control preference. Patients with clinical benefit after 10 cycles of doxorubicin containing-combination will continue on single agent PM01183 or CV, until PD or unacceptable toxicity.
Interim safety analysis will be performed after 150 pts by an independent data monitoring committee. The most relevant inclusion criteria are: pts =18 years old; confirmed diagnosis of SCLC (small-cell carcinomas from unknown site are eligible provided =50% Ki-67 expression). One prior platinum containing regimen is mandatory (additional immunotherapy is allowed provided that it was not given in combination with CT); PS: 0-2 and adequate major organ function, including normal LVEF =50% at baseline. Pts are excluded if pre-treated with PM01183, doxorubicin or topotecan; symptomatic or steroid requiring CNS involvement or any serious medical condition that might preclude safe compliance with study treatment.
The primary objective is to determine a difference in progression-free survival by an independent review committee. Secondary endpoints are overall survival, survival rates at 12/18/24 months, antitumor response (RECIST v1.1), duration of response, QoL, safety, subgroup analyses and pharmacokinetics (PK) of PM01183/doxorubicin arm.
First patient is planned in JUL2016. Enrollment is expected to be completed by 4Q17.
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More Information :
Administrative Data | |
|---|---|
| Organization name | PharmaMar |
| Organization study ID | PM1183-C-003-14 |
| Sponsor | PharmaMar |
| Health Authority | United States: Food and Drug Administration |
| Health Authority | Lebanon: Ministry of Public Health |
| Health Authority | Hungary: National Institute of Pharmacy |
| Health Authority | Canada: Health Canada |
| Health Authority | Czech Republic: State Institute for Drug Control |
| Health Authority | Austria: Austrian Federal Office for Safety in Health Care |
| Health Authority | Belgium: Federal Agency for Medicines and Health Products, FAMHP |
| Health Authority | Brazil: National Health Surveillance Agency |
| Health Authority | Portugal: INFARMED, National Authority of Medicines and Health Products, IP |
| Health Authority | Spain: Agencia Española de Medicamentos y Productos Sanitarios |
| Health Authority | Greece: National Organization of Medicines |
| Health Authority | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
| Health Authority | Germany: Federal Institute for Drugs and Medical Devices |
| Health Authority | Italy: The Italian Medicines Agency |
| Health Authority | Bulgaria: Bulgarian Drug Agency |