AACR Center for Cancer Clinical Trials Announces First Patient Enrolled in Phase II Clinical Trial for Locally Advanced Gastroesophageal Cancer

First-ever AACR-sponsored clinical trial will test whether biomarker-directed treatment approaches can help patients skip surgery and preserve their organs

PHILADELPHIA – The AACR Center for Cancer Clinical Trials, led by the American Association for Cancer Research (AACR), today announced that the AACR Adaptive Biomarker-Driven Organ Preservation Trial in Gastroesophageal Adenocarcinomas (AACR-ADOPT-GEA) has enrolled its first patient. AACR-ADOPT-GEA is a first-of-its-kind phase II clinical trial testing a personalized treatment approach for patients with localized or locally advanced stomach or esophageal cancer to determine its potential to spare patients from life-altering surgery.

This prospective, multicenter, adaptive platform trial was devised by an AACR steering committee composed of leading experts in gastrointestinal cancers, including oncologists, pathologists, and a biostatistician. The trial brings together multiple partners to evaluate whether biomarker-matched targeted therapies currently approved for metastatic gastroesophageal adenocarcinoma (GEA) are effective against earlier-stage GEA.

The study is the first clinical trial sponsored by the AACR Center for Cancer Clinical Trials, which AACR formed in 2023 to leverage the scientific expertise and reach of its membership to improve the lives of patients with cancer.

“As the world’s first and largest cancer research organization, AACR is uniquely positioned to take this bold new step toward advancing patient care,” said AACR Chief Executive Officer Margaret Foti, PhD, MD (hc). “Through the AACR Center for Cancer Clinical Trials, AACR will draw from its more than 65,000 members, including representatives from academia, the pharmaceutical industry, and patient advocacy organizations, to ensure its clinical trials are scientifically rigorous, clinically impactful, and patient centered.”

“While AACR will always be the home for discovery science, we are excited to enter a new chapter with the launch of the AACR Center for Cancer Clinical Trials to apply basic science discoveries to innovative clinical strategies,” said AACR Clinical Trials Advisory Council Chair and former AACR President Patricia M. LoRusso, DO, PhD (hc), FAACR.

“GEA is a devastating disease with fewer than 40% of patients alive five years after diagnosis,” continued LoRusso, who is the chief of experimental therapeutics at Yale School of Medicine. “The current standard of care for nonmetastatic disease has debilitating consequences for the patient’s quality of life, underscoring the high unmet need for novel therapeutic approaches to this cancer—a need that AACR-ADOPT-GEA aims to address.”

Currently, most patients with localized or locally advanced GEA undergo neoadjuvant chemotherapy followed by surgical removal of their stomach or esophagus. The surgeries, known as gastrectomy or esophagectomy, have a severe impact on quality of life, including requiring patients to sleep in an inclined position and avoid full-sized meals for the rest of their lives.

GEAs have diverse molecular features, and treatment strategies tailored to a tumor’s specific biomarkers have been effective against metastatic GEA. However, their efficacy in earlier stages of the disease remains unclear.

In AACR-ADOPT-GEA, patients with resectable stage 2-3 GEA will receive neoadjuvant treatment with therapeutics matched to their tumor: zanidatamab (Ziihera), tislelizumab (Tevimbra), and chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive tumors; or zolbetuximab (Vyloy), tislelizumab, and chemotherapy for claudin 18.2 (CLDN18.2)-positive tumors. In the future, as new therapies are added to the study platform, patients with other alterations in their tumors will also be enrolled.

Using a two-stage design, the study aims first to assess the ability of each treatment to shrink or eliminate the tumor, as measured by pathologic complete response (pCR), as well as to develop a signature to predict which patients have a pCR. In the second stage, another set of patients will undergo treatment with the regimen matched to their tumor, and those predicted to have a pCR based on the developed signature will skip surgery. Treatments that enable at least 20% of patients to avoid surgery will advance from the platform for future study. In both stages of the trial, patients will be followed for several years to assess short-term and long-term outcomes.

As the trial’s sponsor, AACR is dedicated to ensuring that the study will catalyze further insights into GEA by incorporating the collection and analysis of patient tissue and blood samples before, during, and after treatment. These samples will provide critical information that researchers can take back to the bench to identify biomarkers of response and resistance, laying the foundation for future lifesaving advances against this often-deadly disease.

“The AACR-ADOPT-GEA trial has the potential to establish an entirely novel clinical strategy for GEA patients that will strive to preserve the stomach or esophagus in some patients through a sophisticated molecularly customized clinical approach,” said Jaffer A. Ajani, MD, co-principal investigator of the trial and a gastrointestinal medical oncologist and professor at The University of Texas MD Anderson Cancer Center. “In the future, this innovative organ preservation strategy could be applied to patients with other tumor types, such as rectal, bladder, breast, or lung.” 

“To date, perioperative studies in patients with GEA have applied a one-size-fits-all approach, with all patients being treated in the same way regardless of the molecular markers their tumors express and all these patients ultimately needing a large surgical procedure to achieve cure. The AACR-ADOPT-GEA study is a departure from this paradigm,” said Elena Elimova, MD, who is co-principal investigator of the trial, a gastrointestinal medical oncologist at the Princess Margaret Cancer Centre, and an associate professor at the University of Toronto. “Additionally, the adaptive design allows for rapid assessment of novel or targeted therapies in the curative setting, where they can potentially have the most impact.”

AACR-ADOPT-GEA (NCT07290985) is sponsored by AACR and is conducted in collaboration with Jazz Pharmaceuticals; BeOne Medicines Ltd.; Astellas Pharma Inc.; Natera, Inc.; and Roche Diagnostics.