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Purpose

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

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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)

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

More Details

Status
Terminated
Sponsor
Elevation Oncology

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.