A Safety, Tolerability, and Pharmacokinetics Study of AMG 794 With Claudin 6-positive Non-squamous Non-small Cell Lung Cancer or Epithelial Ovarian Cancer.

Sponsor

Amgen (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05317078

Collaborator

(none)

Enrollment

Arms

55.9

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-squamous Non-small Cell Lung Cancer Epithelial Ovarian Cancer	Drug: AMG 794	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

98 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1 First-In-Human Study to Explore the Safety, Tolerability, and Pharmacokinetics of AMG 794 in Subjects With Claudin 6-positive Advanced/Metastatic Non-squamous Non-small Cell Lung Cancer or Epithelial Ovarian Cancer.

Anticipated Study Start Date :

Oct 24, 2022

Anticipated Primary Completion Date :

Dec 7, 2025

Anticipated Study Completion Date :

Jun 22, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: AMG 794 Monotherapy Dose Exploration Participants with claudin 6-positive advanced/metastatic non-squamous non-small cell lung cancer (NSCLC) or epithelial ovarian cancer (EOC) will be treated in up to 8 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 Short-term intravenous (IV) infusion.
Experimental: Part 2: AMG 794 Monotherapy Dose Expansion Participants with claudin 6-positive advanced/metastatic NSCLC or EOC will be treated with the OBD of AMG 794 identified in Part 1.	Drug: AMG 794 Short-term intravenous (IV) infusion.

Arm

Intervention/Treatment

Experimental: Part 1: AMG 794 Monotherapy Dose Exploration

Participants with claudin 6-positive advanced/metastatic non-squamous non-small cell lung cancer (NSCLC) or epithelial ovarian cancer (EOC) will be treated in up to 8 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

Short-term intravenous (IV) infusion.

Experimental: Part 2: AMG 794 Monotherapy Dose Expansion

Participants with claudin 6-positive advanced/metastatic NSCLC or EOC will be treated with the OBD of AMG 794 identified in Part 1.

Drug: AMG 794

Short-term intravenous (IV) infusion.

Outcome Measures

Primary Outcome Measures

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) [Day 1 to a maximum of 2 years]
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.
Number of Participants Who Experience a Treatment-related AE [Day 1 to a maximum of 2 years]

Secondary Outcome Measures

Minimum Efficacious Dose (MED) [Day 1 to a maximum of 2 years]
Defined as the first unconfirmed partial response (PR) or better.
Maximum Observed Serum Concentration (Cmax) of AMG 794 [Cycle 1 Day 1 to Cycle 5 Day 1 (28 day cycle length)]
Minimum Observed Serum Concentration (Cmin) of AMG 794 [Cycle 1 Day 1 to Cycle 5 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 5 Day 1 (28 day cycle length)]
Confirmed objective response (OR) [Day 1 to a maximum of 2 years]
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).
Confirmed OR [Day 1 to a maximum of 2 years]
Defined as immune BOR (iBOR) of immune CR (iCR) or immune PR (iPR) based on Immune RECIST (iRECIST).
Cancer Antigen (CA) 125 Response [Day 1 to a maximum of 2 years]
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.
Duration of Response [Day 1 to a maximum of 2 years]
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.
Time to Progression [Day 1 to a maximum of 2 years]
Defined as the time from enrollment until the first documentation of radiological disease progression.
Progression-free Survival (PFS) [Day 1 to a maximum of 2 years]
Defined as the time from enrollment until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first.
1-year Overall Survival (OS) [1 year]
2-year OS [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Pre-screening:

Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 -1.
Participants with histologically or cytologically documented non-squamous NSCLC or EOC that is metastatic or unresectable.

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 non-squamous NSCLC or EOC that is metastatic or unresectable at screening time point. Participants should have exhausted available standard of care systemic therapy or should not be candidates for such available therapy.
Available positive test result for claudin 6 expression resulting from testing of an available archival tissue sample in pre-screening or obtained from biopsy in a screening procedure.
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.
Ongoing or active infection requiring IV anti-infective therapy less than 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.
History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless agreed upon with Medical Monitor and meeting the following criteria:
Negative test for SARS-CoV-2 ribonucleic acid by reverse transcriptase-polymerase chain reaction within 72 hours of first dose of investigational product (IP).
No acute symptoms of coronavirus (COVID-19) disease within 10 days prior to first dose of IP (counted from day of positive test for asymptomatic participants).
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.
Pregnancy and contraception.
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.