Digestive System Neoplasm, Gastrointestinal Neoplasms, Neoplasms, Neoplasms by Site, Stomach Neoplasm
Conditions
Keywords
Gastric Cancer, Gastroesophageal Junction (GEJ) Adenocarcinoma
Brief summary
This study is an open-label, international, multi-center, Phase 1 study in adult patients with solid tumors likely to express CLDN18.2.
Interventions
DRUGEO-3021
Anti-Claudin 18.2 antibody drug conjugate
VEGFR2 inhibitor
DRUGDostarlimab
anti-PD-1 antibody
Sponsors
Eli Lilly and Company
GlaxoSmithKline
CSPC Pharmaceutical Group Limited
Elevation Oncology
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Up to 24 months | 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. |
Countries
Japan, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EO-3021 Monotherapy 1.0 mg/kg In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma received EO-3021 monotherapy 1.0 mg/kg every 3 weeks to determine MTD/RP2D(s).
EO-3021: Anti-Claudin 18.2 antibody drug conjugate | 3 |
| EO-3021 Monotherapy 2.0 mg/kg In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma received EO-3021 monotherapy 2.0 mg/kg every 3 weeks to determine MTD/RP2D(s).
In expansion, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma expressing CLDN18.2 who had received at least 1 but no more than 3 prior lines of therapy in the advanced metastatic setting were randomized to EO-3021 2.0 mg/kg or 2.5 mg/kg every 3 weeks in a 1:1 fashion.
EO-3021: Anti-Claudin 18.2 antibody drug conjugate | 42 |
| EO-3021 Monotherapy 2.5 mg/kg In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma received EO-3021 monotherapy 2.5 mg/kg every 3 weeks to determine MTD/RP2D(s).
In expansion, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma expressing CLDN18.2 who had received at least 1 but no more than 3 prior lines of therapy in the advanced metastatic setting were randomized to EO-3021 2.0 mg/kg or 2.5 mg/kg every 3 weeks in a 1:1 fashion.
EO-3021: Anti-Claudin 18.2 antibody drug conjugate | 34 |
| EO-3021 Monotherapy 2.9 mg/kg In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma received EO-3021 monotherapy 2.9 mg/kg every 3 weeks to determine MTD/RP2D(s).
EO-3021: Anti-Claudin 18.2 antibody drug conjugate | 6 |
| EO-3021 2.0 mg/kg in Combination With Ramucirumab In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma received EO-3021 2.0 mg/kg in combination with ramucirumab every 3 weeks to determine MTD/RP2D(s).
EO-3021: Anti-Claudin 18.2 antibody drug conjugate
Ramucirumab (CYRAMZA®): VEGFR2 inhibitor | 2 |
| EO-3021 2.0 mg/kg in Combination With Dostarlimab In escalation, adult patients with advanced unresectable or metastatic gastric/GEJ adenocarcinoma will receive EO-3021 2.0 mg/kg in combination with dostarlimab every 3 weeks to determine MTD/RP2D(s).
EO-3021: Anti-Claudin 18.2 antibody drug conjugate
Dostarlimab: anti-PD-1 antibody | 1 |
| Total | 88 |
Baseline characteristics
| Characteristic | EO-3021 Monotherapy 1.0 mg/kg | Total | EO-3021 2.0 mg/kg in Combination With Dostarlimab | EO-3021 2.0 mg/kg in Combination With Ramucirumab | EO-3021 Monotherapy 2.9 mg/kg | EO-3021 Monotherapy 2.5 mg/kg | EO-3021 Monotherapy 2.0 mg/kg |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 67.3 years | 60.8 years | 45. years | 46.0 years | 65.7 years | 60.7 years | 60.8 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0.0 Participants | 0 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants |
| Race (NIH/OMB) Asian | 0.0 Participants | 36 Participants | 0.0 Participants | 0.0 Participants | 3.0 Participants | 16.0 Participants | 17.0 Participants |
| Race (NIH/OMB) Black or African American | 0.0 Participants | 3 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants | 1.0 Participants | 2.0 Participants |
| Race (NIH/OMB) More than one race | 0.0 Participants | 0 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0.0 Participants | 0 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0.0 Participants | 5 Participants | 0.0 Participants | 0.0 Participants | 0.0 Participants | 2.0 Participants | 3.0 Participants |
| Race (NIH/OMB) White | 3.0 Participants | 44 Participants | 1.0 Participants | 2.0 Participants | 3.0 Participants | 15.0 Participants | 20.0 Participants |
| Sex: Female, Male Female | 2.0 Participants | 28 Participants | 1.0 Participants | 1.0 Participants | 1.0 Participants | 8.0 Participants | 15.0 Participants |
| Sex: Female, Male Male | 1.0 Participants | 60 Participants | 0.0 Participants | 1.0 Participants | 5.0 Participants | 26.0 Participants | 27.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 29 / 42 | 19 / 34 | 4 / 6 | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 3 / 3 | 42 / 42 | 34 / 34 | 6 / 6 | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 2 / 3 | 20 / 42 | 15 / 34 | 4 / 6 | 0 / 2 | 0 / 1 |
Outcome results
Primary
Number of Patients With Clinically Significant Changes in Laboratory Tests When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.
Time frame: 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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EO-3021 Monotherapy 1.0 mg/kg | Number of Patients With Clinically Significant Changes in Laboratory Tests When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 0.0 Participants |
| EO-3021 Monotherapy 2.0 mg/kg | Number of Patients With Clinically Significant Changes in Laboratory Tests When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 3.0 Participants |
| EO-3021 Monotherapy 2.5 mg/kg | Number of Patients With Clinically Significant Changes in Laboratory Tests When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 2.0 Participants |
| EO-3021 Monotherapy 2.9 mg/kg | Number of Patients With Clinically Significant Changes in Laboratory Tests When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 0.0 Participants |
| EO-3021 2.0 mg/kg in Combination With Ramucirumab | Number of Patients With Clinically Significant Changes in Laboratory Tests When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 0.0 Participants |
| EO-3021 2.0 mg/kg in Combination With Dostarlimab | Number of Patients With Clinically Significant Changes in Laboratory Tests When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 0.0 Participants |
Primary
Number of Patients With Clinically Significant Changes to Vital Signs When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab
Time frame: 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EO-3021 Monotherapy 1.0 mg/kg | Number of Patients With Clinically Significant Changes to Vital Signs When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab | 0.0 Participants |
| EO-3021 Monotherapy 2.0 mg/kg | Number of Patients With Clinically Significant Changes to Vital Signs When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab | 3.0 Participants |
| EO-3021 Monotherapy 2.5 mg/kg | Number of Patients With Clinically Significant Changes to Vital Signs When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab | 2.0 Participants |
| EO-3021 Monotherapy 2.9 mg/kg | Number of Patients With Clinically Significant Changes to Vital Signs When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab | 0.0 Participants |
| EO-3021 2.0 mg/kg in Combination With Ramucirumab | Number of Patients With Clinically Significant Changes to Vital Signs When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab | 0.0 Participants |
| EO-3021 2.0 mg/kg in Combination With Dostarlimab | Number of Patients With Clinically Significant Changes to Vital Signs When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab | 0.0 Participants |
Primary
Number of Patients With Serious Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.
Time frame: 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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EO-3021 Monotherapy 1.0 mg/kg | Number of Patients With Serious Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 2.0 Participants |
| EO-3021 Monotherapy 2.0 mg/kg | Number of Patients With Serious Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 20.0 Participants |
| EO-3021 Monotherapy 2.5 mg/kg | Number of Patients With Serious Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 15.0 Participants |
| EO-3021 Monotherapy 2.9 mg/kg | Number of Patients With Serious Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 4.0 Participants |
| EO-3021 2.0 mg/kg in Combination With Ramucirumab | Number of Patients With Serious Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 0.0 Participants |
| EO-3021 2.0 mg/kg in Combination With Dostarlimab | Number of Patients With Serious Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 0.0 Participants |
Primary
Number of Patients With Treatment Emergent Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab.
Time frame: 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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EO-3021 Monotherapy 1.0 mg/kg | Number of Patients With Treatment Emergent Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 3.0 Participants |
| EO-3021 Monotherapy 2.0 mg/kg | Number of Patients With Treatment Emergent Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 42.0 Participants |
| EO-3021 Monotherapy 2.5 mg/kg | Number of Patients With Treatment Emergent Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 34.0 Participants |
| EO-3021 Monotherapy 2.9 mg/kg | Number of Patients With Treatment Emergent Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 6.0 Participants |
| EO-3021 2.0 mg/kg in Combination With Ramucirumab | Number of Patients With Treatment Emergent Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 2.0 Participants |
| EO-3021 2.0 mg/kg in Combination With Dostarlimab | Number of Patients With Treatment Emergent Adverse Events When Treated With EO-3021 as Monotherapy and in Combination With Ramucirumab or Dostarlimab. | 1.0 Participants |
Primary
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.
Time frame: Up to 24 months
Population: The Efficacy Evaluable Population includes all patients who receive at least one dose of EO-3021, have baseline measurable disease and at least one post baseline imaging assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EO-3021 Monotherapy 1.0 mg/kg | The Estimate of Overall Response Rate (ORR) for the Efficacy Population. | 1 Participants |
| EO-3021 Monotherapy 2.0 mg/kg | The Estimate of Overall Response Rate (ORR) for the Efficacy Population. | 5 Participants |
| EO-3021 Monotherapy 2.5 mg/kg | The Estimate of Overall Response Rate (ORR) for the Efficacy Population. | 4 Participants |
| EO-3021 Monotherapy 2.9 mg/kg | The Estimate of Overall Response Rate (ORR) for the Efficacy Population. | 0 Participants |
| EO-3021 2.0 mg/kg in Combination With Ramucirumab | The Estimate of Overall Response Rate (ORR) for the Efficacy Population. | 0 Participants |
| EO-3021 2.0 mg/kg in Combination With Dostarlimab | The Estimate of Overall Response Rate (ORR) for the Efficacy Population. | 1 Participants |
Primary
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.
Time frame: The first 21-day treatment cycle for each patient enrolled in the Escalation Phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EO-3021 Monotherapy 1.0 mg/kg | 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. | 0.0 Participants |
| EO-3021 Monotherapy 2.0 mg/kg | 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. | 0.0 Participants |
| EO-3021 Monotherapy 2.5 mg/kg | 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. | 2.0 Participants |
| EO-3021 Monotherapy 2.9 mg/kg | 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. | 5.0 Participants |
| EO-3021 2.0 mg/kg in Combination With Ramucirumab | 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. | 0.0 Participants |
| EO-3021 2.0 mg/kg in Combination With Dostarlimab | 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. | 0.0 Participants |