Study of EO-3021 in Adult Patients With Solid Tumors Likely to Express CLDN18.2

A Phase 1 Dose Escalation and Expansion Study of EO-3021, an Anti-claudin 18.2 (CLDN18.2) Antibody Drug Conjugate, in Patients With Solid Tumors Likely to Express CLDN18.2

This study is an open-label, international, multi-center, Phase 1 study in adult patients with solid tumors likely to express CLDN18.2.

Study Overview

• Status: Terminated
• Conditions: Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasm; Stomach Neoplasm
• Intervention / Treatment: Drug: EO-3021; Drug: Ramucirumab (CYRAMZA®); Drug: Dostarlimab

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• South Korea
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Yonsei University
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale - Smilow Cancer Hospital
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University
    • Washington D.C., District of Columbia, United States, 20016
      • Johns Hopkins University - Sibley Memorial Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Orlando, Florida, United States, 32827
      • Sarah Cannon Research Institute at Florida Cancer Specialists
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Cancer
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Atrium Health/Wake Forest University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • UW Carbone Cancer Center - Cancer Connect

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Availability of tumor tissue for evaluation of biomarker
• Patients enrolled to expansion must have tumors expressing CLDN 18.2 based on central prospective IHC testing.

• Histologically and/or cytologically confirmed diagnosis of advanced metastatic gastric/GEJ adenocarcinoma not amenable to resection or radiation therapy with curative intent

  •≥ 18 years of age

• ECOG performance status (PS) 0 or 1 at Screening
• Progressed on or after standard therapy, or are intolerable of available standard therapy, or there is no available standard therapy
• In dose escalation, there is no limit on the number of prior lines of therapy.
• In expansion, for EO-3021 monotherapy, at least 1 but no more than 3 prior lines of therapy in the advanced/metastatic setting is allowed
• In expansion, for EO-3021 in combination with ramucirumab, only 1 prior line of therapy in the advanced/metastatic setting is allowed. Prior fluoropyrimidine and platinum-containing chemotherapy is required
• In expansion, for EO-3021 in combination with dostarlimab, no prior systemic therapy in the advanced/metastatic setting is allowed.
• Have at least one measurable extra-cranial lesion as defined by RECIST v1.1
• Adequate organ function
• Life expectancy > 12 weeks
• Ability to understand the nature of this study, comply with protocol requirements, and give written informed consent
• Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 6 months following study completion (or longer if required by local regulation)

Key Exclusion Criteria:

• Pregnant or breastfeeding
• Symptomatic or untreated brain metastases
• Have previously received CLDN18.2 antibody drug conjugates (ADCs) or any ADC containing an auristatin payload (prior monoclonal antibody against CLDN18.2 may be eligible)
• Have peripheral neuropathy Grade ≥2
• Have history of non-infectious pneumonitis/interstitial lung disease
• Have diagnosis of another malignancy, or history of systemic treatment for invasive cancer within last 3 years. Note: Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. Diagnosis of non-melanoma skin cancer, carcinoma in situ of the cervix or breast, or noninvasive tumor does not affect eligibility
• Have active ocular surface disease at baseline (based on screening ophthalmic examination) as defined as symptomatic or Grade ≥2 disease involving the cornea
• Have history of Grade ≥2 gastritis
• Have serious concurrent illness or clinically relevant active bacterial, fungal or viral infection
• Have a history of several allergic and/or anaphylactic reactions to known chimeric, human, or humanized antibodies, fusion proteins or known allergies to components of EO-3021, ramucirumab, or dostarlimab
• Clinically significant cardiac disease, including but not limited to symptomatic congestive heart failure, unstable angina, acute myocardial infarction within 6 months of planned first dose, or unstable cardiac arrhythmia requiring therapy (including torsades de pointes)
• Have history of allogenic hematopoietic stem cell transplantation or solid organ transplantation with ongoing systemic immunosuppressive therapy
• Received any live vaccine within 30 days of enrollment
• Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the Investigator
• Expansion only: Have HER2+ disease as defined by American Society of Clinical Oncology-College of American Pathologists guidelines for gastric/GEJ adenocarcinoma
• Ramucirumab Arms Only: Received prior treatment with ramucirumab and other VEGFR2 inhibitors
• Dostarlimab Arms Only: Prior treatment with immune checkpoint inhibitors (ICI) including dostarlimab and other anti-PD-1, anti-PD-L1, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EO-3021 Monotherapy; In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma will receive EO-3021 monotherapy at various doses every 3 weeks to determine MTD/RP2D(s). In expansion, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma expressing CLDN18.2 who have received one and no more than three lines of prior systemic therapy in the advanced metastatic setting will be randomized to one of two doses of EO-3021 dosed every 3 weeks to confirm RP2D.	Drug: EO-3021; Anti-Claudin 18.2 antibody drug conjugate
Experimental: EO-3021 in combination with ramucirumab; In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma will receive EO-3021 at various doses in combination with ramucirumab every 3 weeks to determine MTD/RP2D(s). In expansion, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma expressing CLDN18.2 who have received only one prior systemic therapy in the advanced metastatic setting will be treated with EO-3021 in combination with ramucirumab every 3 weeks to confirm RP2D.	Drug: EO-3021; Anti-Claudin 18.2 antibody drug conjugate; Drug: Ramucirumab (CYRAMZA®); VEGFR2 inhibitor
Experimental: EO-3021 in combination with dostarlimab; In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma will receive EO-3021 at various doses in combination with dostarlimab every 3 weeks to determine MTD/RP2D(s). In expansion, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma expressing CLDN18.2 who have not received any prior systemic therapies in the advanced metastatic setting will be treated with EO-3021 in combination with dostarlimab every 3 weeks to confirm RP2D.	Drug: EO-3021; Anti-Claudin 18.2 antibody drug conjugate; Drug: Dostarlimab; anti-PD-1 antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Treatment Emergent Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.		From the time of informed consent, for approximately 12 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
The Incidence Rate of Dose Limiting Toxicities (DLT) During the First 21-day Cycle of Treatment With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.		The first 21-day treatment cycle for each patient enrolled in the Escalation Phase
Number of Patients With Serious Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.		From the time of informed consent, for approximately 12 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
Number of Patients With Clinically Significant Changes to Vital Signs When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab		From the time of informed consent, for approximately 12 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose
Number of Patients With Clinically Significant Changes in Laboratory Tests When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.		From the time of informed consent, for approximately 12 months (or earlier if the participant discontinues from the study), and through Safety Follow-up (28 days after the last dose)
The Estimate of Overall Response Rate (ORR) for the Efficacy Population.	Tumor assessments were evaluated at baseline by computerized tomography (CT) or magnetic resonance imaging (MRI). The primary objective of this study was to determine the overall objective response rate (ORR) per investigator assessment, defined as confirmed complete response (CR; disappearance of all target lesions) + partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) by RECIST v1.1.	Up to 24 months

Collaborators and Investigators

• Sponsor: Elevation Oncology
• Collaborators: Eli Lilly and Company; GlaxoSmithKline; CSPC Pharmaceutical Group Limited
• Investigators: Study Director: Valerie Jansen, MD, PhD, Elevation Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Actual): May 7, 2025
• Study Completion (Actual): June 2, 2025

Study Registration Dates

• First Submitted: July 31, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: October 29, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Gastric Cancer; Gastroesophageal Junction (GEJ) Adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Neoplasms; Stomach Neoplasms; Gastrointestinal Neoplasms; Adenocarcinoma; Digestive System Neoplasms; Neoplasms by Site; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Ramucirumab; dostarlimab
• Other Study ID Numbers: ELVCAP-002-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No