A Phase 1 Safety, Tolerability, and Pharmacokinetics Study of AMG 794 With Claudin 6-positive Non-small Cell Lung Cancer, Epithelial Ovarian Cancer, and Other Malignant Solid Tumor Indications

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the safety and tolerability of AMG 794 in adult participants and to determine the optimal biological active dose (OBD), at or below the maximum tolerated dose (MTD) with MTD 1 as the maximum tolerated starting dose and MTD 2 as the maximum tolerated target dose.

Official Title
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Phase 1 First-In-Human Study to Explore the Safety, Tolerability, and Pharmacokinetics of AMG 794 in Participants With Claudin 6-positive Advanced/Metastatic Non-small Cell Lung Cancer, Epithelial Ovarian Cancer, and Other Malignant Solid Tumor Indications

Conditions
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Non-squamous Non-small Cell Lung Cancer, Epithelial Ovarian Cancer, Claudin 6-positive Advanced/Metastatic Malignant Solid Tumors

Intervention / Treatment
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* Drug: AMG 794


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-screening: Age ≥ 18 years. Eastern Cooperative Oncology Group (ECOG) performance status of 0 -1. Participants with histologically or cytologically documented malignant solid tumor diseases expressing claudin-6 (CLDN6) including but not limited to NSCLC, EOC, testicular germ cell cancer, uterine endometrial cancer, or triple negative breast cancer, and the cancer is at least either locally advanced or metastatic at pre-screening. Participant has provided informed consent prior to initiation of any study specific activities/procedures. Main study: Age ≥ 18 years. Participant has provided informed consent prior to initiation of any study specific activities/procedures. ECOG performance status of 0 to 1. Participants with histologically or cytologically documented malignant solid tumor diseases expressing CLDN6 including but not limited to NSCLC, EOC, testicular germ cell cancer, uterine endometrial cancer, or triple negative breast cancer, that is metastatic or unresectable at screening time point. Participants should have exhausted available SOC systemic therapy or should not be candidates for such available therapy. For participants enrolling in cohort 3 or higher dose cohort, available positive test result for CLDN6 expression resulting from testing of an available archival tissue sample in pre-screening or obtained from biopsy in a screening procedure. For participants enrolling in cohorts 1, 1a, or 2 during dose escalation, consent to provide archival or fresh tumor tissue slides for immunohistochemistry (IHC) assessment is sufficient and the enrolment is not dependent on availability of the CLDN6 expression test result. For dose expansion cohorts: Participants with at least 1 measurable lesion ≥ 10mm which has not undergone biopsy within 3 months of screening scan. This lesion cannot be biopsied at any time during the study. Life expectancy > 3 months. Adequate organ functions. Exclusion Criteria: Main study: Positive test for human immunodeficiency virus, hepatitis B or hepatitis C. History of other malignancy within the past 2 years. Participant with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection with 1 week prior to administration of a first dose of study treatment Evidence of new or growing central nervous system metastases, leptomeningeal disease, or spinal cord compression. Participants with known brain metastases may be eligible if they completed radiotherapy, surgery or stereotactic surgery for the brain metastases and do not present with neurological symptoms and/or have stable disease assessed by imaging within 4 weeks of signing consent to this study and not requiring acute corticosteroid therapy or steroid taper. Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. Anticancer therapies including radiotherapy, chemotherapy or molecularly targeted treatments or tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever is longer) of administration of a first dose of study treatment; immunotherapies/monoclonal antibodies within 3 weeks of administration of a first dose of study treatment. Has had a major surgery within 4 weeks of administration of a first dose of study treatment (excluded: biopsies and central venous catheter insertion). Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy while on study, (e.g., ulcerative colitis, Crohn's disease). Recent or current use of inhaled steroids or physiological substitution in case of adrenal insufficiency is not exclusionary. Female participants who are of childbearing potential unwilling to use protocol-specified method of contraception, who are breastfeeding and/or planning to become pregnant. Male participants who have a female partner of childbearing potential who are unwilling to practice sexual abstinence or use protocol-specified contraception and/or who are unwilling to abstain from donating sperm. Participant has known sensitivity to any of the products or components to be administered during dosing. Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (e.g., Clinical Outcome Assessments) to the best of the participant and investigator's knowledge. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: AMG 794 Monotherapy Dose Exploration<br>Participants with claudin 6 (CLDN6)-positive advanced/metastatic non-squamous non-small cell lung cancer (NSCLC), epithelial ovarian cancer (EOC), or other solid tumor indications will be treated in up to 11 multiple ascending cohorts with additional participants optionally enrolled in dose exploration cohorts with target dose levels that have previously been shown to be safe and tolerable. | Drug: AMG 794<br>* Short-term intravenous (IV) infusion.<br>|
| Experimental: Part 2: AMG 794 Monotherapy Dose Expansion<br>Participants with CLDN6-positive advanced/metastatic NSCLC, EOC, or other solid tumor indications will be treated with the OBD of AMG 794 identified in Part 1. | Drug: AMG 794<br>* Short-term intravenous (IV) infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experience a Dose Limiting Toxicity (DLT) |  | Day 1 to Day 28 | 
| Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Adverse events (AEs) are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests that occur after study treatment administration will be recorded as TEAEs. | Day 1 to a maximum of 2 years | 
| Number of Participants Who Experience a Treatment-related AE |  | Day 1 to a maximum of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimum Efficacious Dose (MED) | Defined as the first unconfirmed partial response (PR) or better. | Day 1 to a maximum of 2 years | 
| Maximum Observed Serum Concentration (Cmax) of AMG 794 |  | Cycle 1 Day 1 to Cycle 6 Day 1 (28 day cycle length) | 
| Minimum Observed Serum Concentration (Cmin) of AMG 794 |  | Cycle 1 Day 1 to Cycle 6 Day 1 (28 day cycle length) | 
| Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 794 |  | Cycle 1 Day 1 to Cycle 6 Day 1 (28 day cycle length) | 
| Confirmed objective response (OR) | Defined as best overall response [BOR] of complete response [CR] or PR based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). | Day 1 to a maximum of 2 years | 
| Confirmed OR | Defined as immune BOR (iBOR) of immune CR (iCR) or immune PR (iPR) based on Immune RECIST (iRECIST). | Day 1 to a maximum of 2 years | 
| Cancer Antigen (CA) 125 Response | CA 125 response will be analyzed in the Ovarian Cancer Analysis Set, defined as all participants with a primary tumor type of ovarian cancer who are enrolled and receive at least 1 dose of AMG 794. | Day 1 to a maximum of 2 years | 
| Duration of Response | Defined as the time from the first documentation of OR until the first documentation of disease progression or death due to any cause, whichever occurs first. | Day 1 to a maximum of 2 years | 
| Time to Progression | Defined as the time from enrollment until the first documentation of radiological disease progression. | Day 1 to a maximum of 2 years | 
| Progression-free Survival (PFS) | Defined as the time from enrollment until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first. | Day 1 to a maximum of 2 years | 
| 1-year Overall Survival (OS) |  | 1 year | 
| 2-year OS |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant solid tumors, Claudin 6-positive, AMG 794, CLDN6