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

Epithelial Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05317078
• Other study ID #: 20210007
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 28, 2023
• Est. completion date: February 23, 2028

Study information

• Verified date: January 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 98
• Est. completion date: February 23, 2028
• Est. primary completion date: August 10, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Ovarian Epithelial
• Epithelial Ovarian Cancer
• Lung Neoplasms
• Neoplasms
• Non-squamous Non-small Cell Lung Cancer
• Ovarian Neoplasms

Intervention

Drug:
• AMG 794
Short-term intravenous (IV) infusion.

Locations

Country	Name	City	State
Australia	Southern Oncology Clinical Research Unit	Bedford Park	South Australia
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Cabrini Hospital	Malvern	Victoria
Switzerland	Inselspital Bern	Bern
United States	City of Hope National Medical Center	Duarte	California
United States	University of California Los Angeles	Los Angeles	California
United States	University of California Irvine	Orange	California
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experience a Dose Limiting Toxicity (DLT)		Day 1 to Day 28
Primary	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
Primary	Number of Participants Who Experience a Treatment-related AE		Day 1 to a maximum of 2 years
Secondary	Minimum Efficacious Dose (MED)	Defined as the first unconfirmed partial response (PR) or better.	Day 1 to a maximum of 2 years
Secondary	Maximum Observed Serum Concentration (Cmax) of AMG 794		Cycle 1 Day 1 to Cycle 6 Day 1 (28 day cycle length)
Secondary	Minimum Observed Serum Concentration (Cmin) of AMG 794		Cycle 1 Day 1 to Cycle 6 Day 1 (28 day cycle length)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	1-year Overall Survival (OS)		1 year
Secondary	2-year OS		2 years

External Links

•   AmgenTrials clinical trials website