Clinical trial NCT05317078: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2022-04-07
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)
timeFrame: Day 1 to Day 28
measure: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
timeFrame: Day 1 to a maximum of 2 years
measure: Number of Participants Who Experience a Treatment-related AE
timeFrame: Day 1 to a maximum of 2 years
Secondary outcomes:
measure: Minimum Efficacious Dose (MED)
timeFrame: Day 1 to a maximum of 2 years
measure: Maximum Observed Serum Concentration (Cmax) of AMG 794
timeFrame: Cycle 1 Day 1 to Cycle 6 Day 1 (28 day cycle length)
measure: Minimum Observed Serum Concentration (Cmin) of AMG 794
timeFrame: Cycle 1 Day 1 to Cycle 6 Day 1 (28 day cycle length)
measure: Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 794
timeFrame: Cycle 1 Day 1 to Cycle 6 Day 1 (28 day cycle length)
measure: Confirmed objective response (OR)
timeFrame: Day 1 to a maximum of 2 years
measure: Confirmed OR
timeFrame: Day 1 to a maximum of 2 years
measure: Cancer Antigen (CA) 125 Response
timeFrame: Day 1 to a maximum of 2 years
measure: Duration of Response
timeFrame: Day 1 to a maximum of 2 years
measure: Time to Progression
timeFrame: Day 1 to a maximum of 2 years
measure: Progression-free Survival (PFS)
timeFrame: Day 1 to a maximum of 2 years
measure: 1-year Overall Survival (OS)
timeFrame: 1 year
measure: 2-year OS
timeFrame: 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Bedford Park
country: Australia
facility: Southern Oncology Clinical Research Unit
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Hospital
state: Victoria
city: Bern
country: Switzerland
facility: Inselspital Bern
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: