EO-3021 Elicits Responses in Advanced CLDN18.2+ Gastric/GEJ Cancer

Enrollment will soon begin for the dose-expansion portion of the ongoing phase 1 trial assessing EO-3021 in CLDN18.2-positive tumors.

Treatment with EO-3021 (SYSA1801) produced promising preliminary data in a small cohort of patients with advanced, unresectable, or metastatic gastric or gastroesophageal junction (GEJ) cancers expressing Claudin 18.2 (CLDN18.2), according to dose-escalation findings from a phase 1 trial (NCT05980416).¹

Among 15 patients with evaluable gastric or GEJ cancers, 7 (47%) had CLDN18.2 expression in at least 20% of tumor cells at a data cutoff date of June 10, 2024.

The objective response rate (ORR) among those with CLDN18.2 expression was 42.8%, which included partial responses (PRs) in 3 patients. Additionally, treatment yielded a disease control rate (DCR) of 71.4%, which included stable disease in 2 patients. Among 8 patients with CLDN18.2 expression in less than 20% of tumor cells, the ORR and DCR were 0% and 50%, respectively.

Investigators reported no grade 4/5 treatment-related adverse effects (TRAEs), and less than 10% of patients discontinued study treatment due to toxicity. Frequent treatment-emergent AEs (TEAEs) included nausea (56%), decreased appetite (47%), fatigue (41%), and diarrhea (28%). No patients experienced neutropenia, peripheral neuropathy, or hypoesthesia.

There were 4 dose-limiting toxicities at the 2.9-mg/kg dose level, which included grade 3 fatigue (n = 1), grade 3 encephalopathy (n = 1), grade 3 worsening decreased appetite (n = 1), and grade 2 appetite decrease (n = 1). Based on these toxicities, investigators opted to evaluate the 2.0-mg/kg and 2.5-mg/kg dose levels once every 3 weeks as part of the dose-expansion portion of the trial.

Moving forward, investigators plan to initiate enrollment for the dose-expansion portion of the ongoing phase 1 trial. Developers also intend to expand the trial to include combination cohorts assessing EO-3021 plus ramucirumab (Cyramza) in the second-line setting. Treatment with EO-3021 plus dostarlimab-gxly (Jemperli) will also be evaluated in the first-line setting.

“Gastric and GEJ cancers are devastating diseases, which occur frequently in the [United States] and globally and which, despite recent advancements, still have high levels of mortality. There is a particular need for highly selective therapies that benefit patients with [CLDN18.2]-expressing tumors,” lead investigator Kohei Shitara, MD, chief in the Department of Gastrointestinal Oncology at National Cancer Center Hospital East in Kashiwa, Japan, said in the press release.¹ “To that end, I am excited by the initial data with EO-3021, which suggest it could change the treatment paradigm for a significant portion of patients with gastric or GEJ cancer. I am excited to evaluate EO-3021 in the expansion portion of this phase 1 clinical trial.”

In the dose-escalation portion of this phase 1 trial, 32 patients received EO-3021 at 4 dose levels ranging from 1.0 mg/kg to 2.9 mg/kg every 3 weeks. Of these patients, 26 had gastric or GEJ cancer. Additionally, the median age was 65 years (range, 45-83), and patients received a median of 3 prior lines of therapy (range, 1-7).

The trial’s primary end points include dose-limiting toxicities, TEAEs, serious AEs, and clinically significant changes in vital signs and laboratory tests.² Patients 18 years and older with select advanced or metastatic solid tumors likely to express CLDN18.2, such as gastric, GEJ, pancreatic, or esophageal cancer are eligible for enrollment on the trial.

“Coupled with the promising antitumor activity reported in patients with gastric or GEJ cancer, the data suggest that EO-3021 is a potential best-in-class [CLDN18.2] antibody drug conjugate. We look forward to advancing into monotherapy dose expansion and initiating our combination cohorts in the months ahead, as well as reporting additional data from our ongoing trial in the first half of 2025,” Valerie Malyvanh Jansen, MD, PhD, chief medical officer at Elevation Oncology, developer of EO-3021, concluded.¹

References

1. Elevation Oncology announces promising initial data from phase 1 clinical trial evaluating EO-3021 in patients with advanced unresectable or metastatic solid tumors likely to express Claudin 18.2. News release. Elevation Oncology, Inc. August 6, 2024. Accessed August 6, 2024. https://tinyurl.com/2p8duddd
2. Study of EO-3021 in adult patients with solid tumors likely to express CLDN18.2. ClinicalTrials.gov. Accessed August 6, 2024. https://tinyurl.com/5n73x6kx