Evofosfamide (TH-302) in combination with gemcitabine in previously untreated patients with metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma: Primary analysis of the randomized, double-blind phase III MAESTRO study.

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
Oral Abstract Session: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 


Poster Board Number: 
Poster Session B Board #A3
J Clin Oncol 34, 2016 (suppl 4S; abstr 193)
Eric Van Cutsem, Heinz-Josef Lenz, Junji Furuse, Josep Tabernero, Volker Heinemann, Tatsuya Ioka, Igor Bazin, Makoto Ueno, Tibor Csõszi, Harpreet Wasan, Bohuslav Melichar, Petr Karasek, Teresa Macarulla, Carmen Guillén Ponce, Ewa Kalinka-Warzocha, Zsolt Horvath, Hans Prenen, Michael Schlichting, Fazal Mehdi, Johanna C. Bendell; University Hospitals Leuven, Leuven, Belgium; USC Norris Comprehensive Cancer Center, Los Angeles, CA; Kyorin University Hospital, Tokyo, Japan; Vall d'Hebron University Hospital, Barcelona, Spain; University of Munich, Munich, Germany; Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan; N. N. Blokhin Russian Cancer Research Center, Moscow, Russia; Kanagawa Cancer Center, Yokohama, Japan; Jász-Nagykun Szolnok Megyei Hetényi Géza Kórház-Rendelointézet, Szolnok, Hungary; Hammersmith Hospital, Imperial College, London, United Kingdom; Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic; Masaryk Memorial Cancer Institute, Brno, Czech Republic; Vall d’Hebron University Hospital, Barcelona, Spain; Hospital Ramón y Cajal, Madrid, Spain; Wojewódzki Szpital Specjalistyczny im. M. Kopernika, Lodz, Poland; Debreceni Egyetem Orvos- és Egészségtudományi Centrum, Debrecen, Hungary; Merck KGaA, Darmstadt, Germany; EMD Serono, Inc., Billerica, MA; Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN

Abstract Disclosures


Background: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage and has poor clinical outcome. Hypoxia is a significant negative prognostic factor in PDAC. Evofosfamide (Evo, previously known as TH-302) is a hypoxia-activated prodrug of bromo-isophosphoramide mustard that is preferentially activated under hypoxic conditions. Combining Evo with gemcitabine (Gem) significantly improved progression-free survival (PFS) in a randomized phase II trial in advanced PDAC (NCT01144455).

Methods: MAESTRO is an international, randomized, double-blind, placebo-controlled phase III trial of Evo/Gem vs Placebo/Gem in patients (pts) with measurable, locally advanced unresectable or metastatic PDAC (NCT01746979). Evo and Gem were administered intravenously at a dose of 340 mg/m2 and 1,000 mg/m2, respectively, on days 1, 8, and 15 of a 28-day cycle. Treatment continued until disease progression. Key eligibility criteria included ECOG PS 0/1 and no neoadjuvant or adjuvant chemotherapy <6 months prior to entry. Key eligibility criteria included ECOG PS 0/1 and no neoadjuvant or adjuvant chemotherapy <6 months prior to entry. The primary endpoint was overall survival (OS) with the study designed to detect a HR of 0.75 with 90% power. Secondary endpoints included PFS and objective response rate (ORR), using a hierarchical testing procedure with a 2-sided α=0.05 at each level to adjust for multiplicity.

Results: 346 pts were randomized to Evo/Gem and 347 to Pla/Gem. Baseline pt characteristics were generally similar between arms.

ITT Population Pla/Gem
Median OS, months (95% CI) 7.6 (6.7, 8.3) 8.7 (7.6, 9.9)
HR: 0.84 (95% CI 0.71, 1.01)
Median PFS, months (95% CI) 3.7 (3.6, 3.8) 5.5 (4.8, 5.6)
HR: 0.77 (95% CI 0.65, 0.92)
ORR, % (95% CI) 15 (12, 19) 19 (15, 24)
OR: 1.31 (95% CI 0.88, 1.95)

Grade ≥3 hematologic events were reported more frequently in pts treated with Evo/Gem than Pla/Gem: neutropenia (32.5% vs 20.8%); thrombocytopenia (31.7% vs 5.6%); anemia (22.2% vs 12.0%).

Conclusions: Although the primary endpoint was not met, Evo/Gem showed signs of antitumor activity. No new clinically significant safety findings were observed. Clinical trial information: NCT01746979