Study of AMG 160 in Subjects With Non-Small Cell Lung Cancer

Phase 1

Terminated

Conditions: Non-small Cell Lung Cancer
NSCLC

Interventions: Drug: AMG 160

Registration Number: NCT04822298

Lead Sponsor: Amgen

Brief Summary: This study aims to evaluate the safety and tolerability of AMG 160 and to evaluate the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

Inclusion Criteria

Participant has provided informed consent prior to initiation of any study specific activities/procedures.
Histologically or cytologically confirmed stage 4 or recurrent non-squamous NSCLC (Part 1); histologically or cytologically. confirmed stage 4 or recurrent NSCLC (Part 2 only, squamous cell histology/cytology allowed in Part 2).
Without a driver mutation: disease progression following at least one line of prior chemotherapy and at least 1 prior anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PDL1) therapy.
With a driver mutation must experience disease progression on at least 1 targeted therapeutic agent to be eligible.
Detectable prostate-specific membrane antigen (PSMA) expression by PSMA positron emission tomography (PET)/computed tomography (CT) imaging.
Measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0- 2.

Exclusion Criteria

Radiographic evidence of intratumor cavitation, major blood vessel invasion or encasement by cancer.
Untreated or symptomatic brain metastases and leptomeningeal disease.
History of hemoptysis within 3 months prior to first dose.
History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn disease).
Myocardial infarction, unstable angina, cardiac arrhythmias requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months prior to start of dosing.
Vasculitis or grade 3/4 gastrointestinal bleeding within 3 months prior to first dose; vascular disease (eg, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months of first dose.
Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to start of dosing.
Interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with treatment.
Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation).
Chronic systemic corticosteroid therapy or any other immunosuppressive therapies unless stopped 7 days prior to first dose.
Any biological therapy or immunotherapy within 3 weeks of start of first dose.
Major surgery within 4 weeks of first dose.
Infection requiring IV antimicrobials for management within 7 days of dosing.
Known human immunodeficiency virus (HIV) infection, hepatitis C infection.
Active autoimmune disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1: Dose Exploration	AMG 160	The dose exploration part of the study will estimate the MTD and/or the RP2D.
Part 2: Dose Expansion - Cohort 1 Non-squamous NSCLC	AMG 160	Participants with non-squamous non-small cell lung cancer (NSCLC) will be administered the RP2D identified from the dose exploration part of the study.
Part 2: Dose Expansion - Cohort 2 Squamous NSCLC	AMG 160	Participants with squamous NSCLC will be administered the RP2D identified from the dose exploration part of the study.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experience One or More Dose-limiting Toxicities (DLT)	Day 1 to Day 28	DLT were defined as any adverse event (AE) with an onset within first 28 days following first dose of AMG 160 meeting pre-specified criteria unless clearly attributable to causes other than AMG 160 treatment.
Number of Participants Who Experience One or More Treatment-emergent AE (TEAE)	Median (min, max) time from first dose to 30 days after the last dose, end of study or start of new anti-cancer therapy; whichever is earlier, was 66 (52, 100) days	An AE is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE is any AE that occurred on or after first dose of study treatment up to 30 days after the last dose or End of Study date or start of new anti-cancer therapy, whichever is earlier. A treatment-related TEAE is any TEAE that, per investigator review, has a reasonable possibility of being caused by the study treatment. Any abnormal vital signs measurement or clinical laboratory test result, including those that worsened from Baseline, that were considered clinically significant in the medical and scientific judgement of the investigator were reported as an AE.

Secondary Outcome Measures

Name	Time	Method
Time to Response Per Modified RECIST v1.1	Median (min, max) time from first dose to end of study was 100 (94, 122) days	Time to response per modified RECIST v1.1 was defined as the interval from study Day 1 to the either CR or PR based on investigator assessment. * CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. * PR: Decrease of 30% or greater in tumor burden compared with baseline. CR/PR must have been confirmed at least 4 weeks later.
Time to Clinical Progression	Median (min, max) time from first dose to end of study was 100 (94, 122) days	Time to clinical progression was defined as the interval from study Day 1 to PD. Time to clinical progression was censored at the last evaluable post-baseline tumor assessment prior to subsequent anti-cancer therapy; otherwise at study Day 1. - PD: Increase of 20% or greater in tumor burden compared with nadir and at least 5 mm absolute increase, or unequivocal progression of non-target lesions, or the presence of new lesions. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and quartiles were estimated using the method by Brookmeyer and Crowley (1982).
Duration of Response (DOR) Per Modified RECIST v1.1	Median (min, max) time from first dose to end of study was 100 (94, 122) days	DOR was defined as the time from the date of an initial objective response per modified RECIST v1.1 to the earlier of soft-tissue progression or death based on investigator assessment. * CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. * PR: Decrease of 30% or greater in tumor burden compared with baseline. CR/PR must have been confirmed at least 4 weeks later. Participants who had not ended their response at the time of analysis had DOR censored at their last evaluable tumor assessment by CT/MRI scan.
Time to Subsequent Therapy	Median (min, max) time from first dose to end of study was 100 (94, 122) days	Time to subsequent therapy was defined as the time from study Day 1 to the time a participant started/received the subsequent cancer therapy/subsequent therapy; otherwise time to subsequent therapy was censored at the last known date of any of the study assessment prior to initiating the subsequent cancer therapy/subsequent therapy. Subsequent therapy was defined any anti-cancer therapies intended to treat NSCLC, or any other anti-cancer therapies started after ending study treatment and prior to End of Study. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and quartiles were estimated using the method by Brookmeyer and Crowley (1982).
Radiographic Progression Free Survival (PFS) Per Modified RECIST v1.1	Median (min, max) time from first dose to end of study was 100 (94, 122) days	Radiographic PFS per modified RECIST v1.1 was defined as the interval from study Day 1 to the earlier of a radiographic progressive disease (PD) or death from any cause, based on investigator assessment; otherwise, radiographic PFS was censored at the last evaluable tumor assessment date. - PD: Increase of 20% or greater in tumor burden compared with nadir and at least 5 mm absolute increase, or unequivocal progression of non-target lesions, or the presence of new lesions. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and quartiles were estimated using the method by Brookmeyer and Crowley (1982).
Clinical PFS Per Modified RECIST v1.1	Median (min, max) time from first dose to end of study was 100 (94, 122) days	Clinical PFS per modified RECIST v1.1 was defined as the interval from study Day 1 to the earlier of a clinical PD or death from any cause, based on investigator assessment; otherwise, clinical PFS was censored at the last evaluable tumor assessment date. - PD: Increase of 20% or greater in tumor burden compared with nadir and at least 5 mm absolute increase, or unequivocal progression of non-target lesions, or the presence of new lesions. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and quartiles were estimated using the method by Brookmeyer and Crowley (1982).
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Median (min, max) time from first dose to end of study was 100 (94, 122) days	ORR per modified RECIST v1.1 was defined as the percentage of participants who achieved a best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment. * CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm. * PR: Decrease of 30% or greater in tumor burden compared with baseline. CR/PR must have been confirmed at least 4 weeks later. Exact 95% confidence interval (CI) was calculated using the Clopper-Pearson method.
Time to Progression Per Modified RECIST v1.1	Median (min, max) time from first dose to end of study was 100 (94, 122) days	Time to progression per modified RECIST v1.1 was defined as the interval from study Day 1 to PD, based on investigator assessment. Time to progression was censored at the last evaluable post-baseline tumor assessment prior to subsequent anti-cancer therapy; otherwise at study Day 1. - PD: Increase of 20% or greater in tumor burden compared with nadir and at least 5 mm absolute increase, or unequivocal progression of non-target lesions, or the presence of new lesions. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and quartiles were estimated using the method by Brookmeyer and Crowley (1982).
Overall Survival (OS)	Median (min, max) time from first dose to end of study was 100 (94, 122) days	Overall survival (OS) was defined as the time from the date of study Day 1 until death due to any cause. OS time (months) = (date of death - study Day 1 + 1) x 12/365.25. Medians and quartiles were estimated using the Kaplan-Meier method. 95% CIs for medians and percentiles were using Greenwood's formula to estimate the standard error of the landmark estimates using the method by Kalbfleisch and Prentice (1980).

Trial Locations

Locations (4): Universitaetsklinikum Allgemeines Krankenhaus Wien
🇦🇹
Wien, Austria
Landeskrankenhaus Salzburg
🇦🇹
Salzburg, Austria
Chris OBrien Lifehouse
🇦🇺
Camperdown, New South Wales, Australia
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States