GI Cancer
INNOVATION
About the INNOVATION Trial
The INNOVATION study is a randomized clinical trial assessing the efficacy of adding pertuzumab to standard chemotherapy plus trastuzumab in patients with HER2-positive gastric and gastroesophageal junction (GEJ) adenocarcinoma. Patients were randomized to receive chemotherapy with trastuzumab alone or in combination with pertuzumab. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), objective response rate (ORR), and safety.
The results showed that the addition of pertuzumab did not significantly improve OS compared to trastuzumab alone. Similarly, no meaningful differences were observed in PFS or ORR between the treatment arms. However, the pertuzumab arm was associated with increased toxicity. These findings were presented at the 2024 ASCO Gastrointestinal Cancers Symposium and discussed by experts including Dr. Amol Akhade and Dr. Anna Dorothea Wagner, highlighting the ongoing challenges in optimizing HER2-targeted strategies in upper GI malignancies.
INNOVATION at a Glance
Design - Randomized Phase II intergroup trial (EORTC-1203; EORTC with the Korean Cancer Study Group and Dutch Upper GI Cancer Group; 172 patients enrolled per CT.gov) in resectable HER2-positive gastric/GEJ adenocarcinoma: perioperative chemotherapy alone, plus trastuzumab, or plus trastuzumab and pertuzumab. Registered primary endpoint: near-complete (major) pathological response rate.
Efficacy - Per the results discussed on this page (ASCO GI 2025), adding pertuzumab to chemotherapy plus trastuzumab did not significantly improve overall survival, and no meaningful differences were seen in PFS or ORR between the treatment arms.
Pathologic response - The trial was designed to detect an increase in major pathological response rate with HER2-targeted therapy added to perioperative chemotherapy (registered primary endpoint per CT.gov); see the trial publications for arm-level response rates - the page does not report them numerically.
Safety - The pertuzumab-containing arm was associated with increased toxicity versus trastuzumab-based therapy alone (per the ASCO GI 2025 presentation).
Regulatory / sponsor - Investigational strategies; EORTC-sponsored academic trial. Trastuzumab (Herceptin) is FDA-approved with chemotherapy for HER2-positive metastatic gastric/GEJ cancer (2010, ToGA); pertuzumab (Perjeta) is not approved in gastric cancer.
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated August 19, 2026.
INNOVATION Frequently Asked Questions
What is the INNOVATION trial?
INNOVATION (EORTC-1203, NCT02205047) is a randomized Phase II intergroup trial run by the EORTC with the Korean Cancer Study Group and the Dutch Upper GI Cancer Group in resectable HER2-positive gastric and gastroesophageal junction adenocarcinoma. Patients were randomized to perioperative chemotherapy alone, chemotherapy plus trastuzumab, or chemotherapy plus trastuzumab and pertuzumab, with major pathological response rate as the registered primary endpoint.
What did the INNOVATION trial show?
Per the results discussed on this page at the 2025 ASCO Gastrointestinal Cancers Symposium (LBA331), adding pertuzumab to chemotherapy plus trastuzumab did not significantly improve overall survival, and no meaningful differences in PFS or ORR were observed between arms - while the pertuzumab arm carried more toxicity. The findings underscore the difficulty of improving on trastuzumab-based therapy in upper GI cancers.
Is trastuzumab or pertuzumab FDA approved for gastric cancer?
Trastuzumab (Herceptin) is FDA-approved in combination with chemotherapy for HER2-positive metastatic gastric/GEJ adenocarcinoma (October 2010, based on the ToGA trial), but the perioperative use tested in INNOVATION is investigational. Pertuzumab (Perjeta) is not FDA-approved for gastric cancer in any setting, and INNOVATION's results do not support adding it.
What is the safety profile of adding pertuzumab in INNOVATION?
The pertuzumab-containing arm was associated with increased toxicity compared with trastuzumab-based treatment without pertuzumab, without a corresponding efficacy gain - a key reason experts viewed the dual HER2-blockade strategy unfavorably in this setting.
Why is the INNOVATION trial important?
INNOVATION is one of the few randomized trials of perioperative HER2-targeted therapy in resectable gastric/GEJ cancer. Its negative result for dual HER2 blockade - echoing pertuzumab's failure in metastatic gastric cancer - helped define the limits of extrapolating HER2 strategies from breast cancer, as discussed by experts including Dr. Amol Akhade and Dr. Anna Dorothea Wagner.