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

NCT05317078 | Terminated Phase 1 FDA Drug

• 1 other identifier: 20210007
• Study Type: interventional
• Target: 3
• Locations: 3 countries
• Sites: 8

Brief Summary

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.

Conditions

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

Keywords

Malignant solid tumors; Claudin 6-positive; AMG 794; CLDN6

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (12)

• Minimum Efficacious Dose (MED)

  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)

  Day 1 to a maximum of 2 years

Study Arms (2)

Cohort 1: AMG 794

EXPERIMENTAL

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

Cohort 1a: AMG 794

EXPERIMENTAL

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

Interventions

AMG 794 DRUG

Short-term intravenous (IV) infusion.

Cohort 1: AMG 794; Cohort 1a: AMG 794

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (8)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California Los Angeles

Los Angeles, California, 90095-1678, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Southern Oncology Clinical Research Unit

Bedford Park, South Australia, 5042, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2022
• First Posted: April 7, 2022
• Study Start: February 28, 2023
• Primary Completion: December 19, 2023
• Study Completion: April 1, 2024
• Last Updated: October 8, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

AU (3); US (4); CH (1)