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

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

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.

Study Overview

• Status: Terminated
• Conditions: Non-squamous Non-small Cell Lung Cancer; Epithelial Ovarian Cancer; Claudin 6-positive Advanced/Metastatic Malignant Solid Tumors
• Intervention / Treatment: Drug: AMG 794

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Southern Oncology Clinical Research Unit
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Malvern, Victoria, Australia, 3144
      • Cabrini Hospital
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90095-1678
      • University of California Los Angeles
    • Orange, California, United States, 92868
      • University of California Irvine
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: AMG 794; Participants were planned to receive the lowest dose (Dose A), as a short-term IV infusion on Cycle 1 Day 1, with an increased dose on Cycle 1 Day 3 (Dose C) and Cycle 1 Day 8 (Dose E). After reaching the highest planned dose for the cohort (Dose E), participants continued to receive short-term IV infusions on Cycle 1 Day 15, then QW thereafter in 28-day cycles. Due to early study termination, participants only received Dose A on Cycle 1 Day 1 and Dose C on Cycle 1 Day 3.	Drug: AMG 794; Short-term intravenous (IV) infusion.
Experimental: Cohort 1a: AMG 794; Participants were planned to receive the lowest dose (Dose A), as a short-term IV infusion on Cycle 1 Day 1, with an increased dose on Cycle 1 Day 8 (Dose B) and Cycle 1 Day 15 (Dose D). After reaching the highest planned dose for the cohort (Dose D), participants continued to receive short-term IV infusions QW thereafter in 28-day cycles.	Drug: AMG 794; Short-term intravenous (IV) infusion.

What is the study measuring?

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
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
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)

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2023
• Primary Completion (Actual): December 19, 2023
• Study Completion (Actual): April 1, 2024

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Estimated): October 8, 2025
• Last Update Submitted That Met QC Criteria: October 7, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Malignant solid tumors; Claudin 6-positive; AMG 794; CLDN6
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: 20210007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2 ) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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