Non-small Cell Lung Cancer, NSCLC
Conditions
Keywords
AMG 160, Phase 1b
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).
Interventions
DRUGAMG 160
AMG 160 administered as an intravenous (IV) infusion
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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 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). |
| 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). |
Countries
Australia, Austria, United States
Participant flow
Recruitment details
This study was conducted at 2 centers in Australia and Austria between 31 August 2021 and 26 January 2022.
Pre-assignment details
The study was terminated early due to sponsor decision after 3 participants were enrolled into Cohort 1 of Part 1 (dose exploration); no participants were screened or enrolled for additional Part 1 or Part 2 (dose expansion) cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: AMG 160 Cohort 1 AMG 160 was administered as a short-term IV infusion every 2 weeks after the target dose was reached. Treatment lasted until disease progression, up to a planned maximum of 3 years from the first dose of AMG 160. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
Baseline characteristics
| Characteristic | Part 1: AMG 160 Cohort 1 |
|---|---|
| Age, Continuous | 58.0 Years STANDARD_DEVIATION 3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 |
Outcome results
Primary
Number of Participants Who Experience One or More Dose-limiting Toxicities (DLT)
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.
Time frame: Day 1 to Day 28
Population: DLT analysis set: defined as all participants that were enrolled and receive at least one dose of AMG 160 with an evaluable DLT endpoint. The DLT endpoint is evaluable if either: 1) the participant experienced a DLT, or 2) the participant did not experience a DLT after receiving all planned doses within the 28-day DLT window.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: AMG 160 Cohort 1 | Number of Participants Who Experience One or More Dose-limiting Toxicities (DLT) | 1 Participants |
Primary
Number of Participants Who Experience One or More Treatment-emergent AE (TEAE)
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.
Time frame: 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
Population: Safety analysis set: defined as all participants that were enrolled and receive at least 1 dose of AMG 160.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: AMG 160 Cohort 1 | Number of Participants Who Experience One or More Treatment-emergent AE (TEAE) | Any TEAEs | 3 Participants |
| Part 1: AMG 160 Cohort 1 | Number of Participants Who Experience One or More Treatment-emergent AE (TEAE) | Any treatment-related TEAEs | 3 Participants |
Secondary
Clinical PFS Per Modified RECIST v1.1
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).
Time frame: Median (min, max) time from first dose to end of study was 100 (94, 122) days
Population: Safety analysis set: defined as all participants that were enrolled and receive at least one dose of AMG 160.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: AMG 160 Cohort 1 | Clinical PFS Per Modified RECIST v1.1 | 3.09 Months |
Secondary
Duration of Response (DOR) Per Modified RECIST v1.1
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 frame: Median (min, max) time from first dose to end of study was 100 (94, 122) days
Population: RECIST v1.1 evaluable analysis set: defined as all participants that are enrolled, receive at least 1 dose of AMG 160 and had measurable baseline disease per RECIST 1.1 per protocol and had the opportunity to be followed for at least 9 weeks starting from study Day 1. Analyzed in participants with an objective response.
Secondary
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
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 frame: Median (min, max) time from first dose to end of study was 100 (94, 122) days
Population: RECIST v1.1 evaluable analysis set: defined as all participants that are enrolled, receive at least 1 dose of AMG 160 and had measurable baseline disease per RECIST 1.1 per protocol and had the opportunity to be followed for at least 9 weeks starting from study Day 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: AMG 160 Cohort 1 | Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0.0 Percentage of Participants |
Secondary
Overall Survival (OS)
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).
Time frame: Median (min, max) time from first dose to end of study was 100 (94, 122) days
Population: Safety analysis set: defined as all participants that were enrolled and receive at least one dose of AMG 160.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: AMG 160 Cohort 1 | Overall Survival (OS) | 3.29 Months |
Secondary
Radiographic Progression Free Survival (PFS) Per Modified RECIST v1.1
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).
Time frame: Median (min, max) time from first dose to end of study was 100 (94, 122) days
Population: Safety analysis set: defined as all participants that were enrolled and receive at least one dose of AMG 160.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: AMG 160 Cohort 1 | Radiographic Progression Free Survival (PFS) Per Modified RECIST v1.1 | 3.29 Months |
Secondary
Time to Clinical Progression
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).
Time frame: Median (min, max) time from first dose to end of study was 100 (94, 122) days
Population: Safety analysis set: defined as all participants that were enrolled and receive at least one dose of AMG 160.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: AMG 160 Cohort 1 | Time to Clinical Progression | NA Months |
Secondary
Time to Progression Per Modified RECIST v1.1
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).
Time frame: Median (min, max) time from first dose to end of study was 100 (94, 122) days
Population: Safety analysis set: defined as all participants that were enrolled and receive at least one dose of AMG 160.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: AMG 160 Cohort 1 | Time to Progression Per Modified RECIST v1.1 | 3.29 Months |
Secondary
Time to Response Per Modified RECIST v1.1
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 frame: Median (min, max) time from first dose to end of study was 100 (94, 122) days
Population: Safety analysis set: defined as all participants that were enrolled and receive at least one dose of AMG 160. Analyzed in participants with an objective response.
Secondary
Time to Subsequent Therapy
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).
Time frame: Median (min, max) time from first dose to end of study was 100 (94, 122) days
Population: Safety analysis set: defined as all participants that were enrolled and receive at least one dose of AMG 160. Analyzed in participants who received subsequent therapy.