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

Elevation Oncology

Status and phase: Terminated; Phase 1

Conditions: Digestive System Neoplasm; Neoplasms; Neoplasms by Site; Stomach Neoplasm; Gastrointestinal Neoplasms

Treatments: Drug: Ramucirumab (CYRAMZA®); Drug: EO-3021; Drug: Dostarlimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05980416

ELVCAP-002-01

Details and patient eligibility

About

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

Enrollment: 88 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 monoclonocal antiboby 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 protiens or known allergiest 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 Ams 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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88 participants in 3 patient groups

EO-3021 Monotherapy

Experimental group

Description:

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.

Treatment:

Drug: EO-3021

EO-3021 in combination with ramucirimab

Experimental group

Description:

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.

Treatment:

Drug: EO-3021

Drug: Ramucirumab (CYRAMZA®)

EO-3021 in combination with dostarlimab

Experimental group

Description:

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 expresssing 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.

Treatment:

Drug: Dostarlimab

Drug: EO-3021