Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Recurrent, progressive, advanced
Brief summary
This is a phase I/II study of erlotinib and AMG 102 in previously treated subjects with advanced NSCLC. Subjects will be enrolled with recurrent or progressive advanced stage NSCLC that has been treated with at least one and a maximum of two prior chemotherapy regimens. The Phase I part of the study will enroll 8-16 subjects with the Phase II part enrolling 21-45 subjects. The Phase I part of the study is designed to determine how safest the combination of AMG 102 and erlotinib is and the recommended dose for the Phase II part. The Phase II part is to determine whether the combination of AMG102 and erlotinib works enough to warrant further interest in this combination.
Detailed description
While modest improvements have been made in survival and quality of life in patients with advanced NSCLC there is a need to explore new agents and combinations with novel mechanisms of action in an effort to improve clinical outcomes in this patient population. The HGF/c-MET pathway inhibition is a promising novel target in NSCLC. Preclinical evidence support the combined targeting of EGFR and HGF/c-MET pathways in NSCLC as a strategy that may result in enhanced antitumor activity. Inhibition of both HGF/c-Met and EGFR pathways can be accomplished by utilizing the combination of AMG 102 and erlotinib in patients with advanced NSCLC. Therefore, we propose a safety and efficacy, phase I/II clinical trial of the combination in patients with previously treated, advanced NSCLC.
Interventions
DRUGAMG 102 and erlotinib
Dose Level -2 Dose level -1 Dose Level 0 AMG 102 5 mg/kg 7.5 mg/kg 15 mg/kg Erlotinib 150 mg 150 mg 150 mg The first cohort of patients in the phase I portion will start at dose level 0 of AMG102.
Sponsors
Amgen
Ahmad Tarhini
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must have baseline evaluations performed prior to the first dose of study drug and must meet all inclusion and
Exclusion criteria
. Results of all baseline evaluations, which assure that all inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants That Experienced a Dose Limiting Toxicity | During first cycle of treatment (3 weeks) | Determination of the safety and recommended phase II dose of AMG 102 when combined with erlotinib for the treatment of patients with advanced, previously-treated NSCLC. |
| Disease Control Rate (DCR) | Six weeks from initiation of treatment with AMG 102 + Erlotinib | Using RECIST v1.1 criteria, DCR was determined by following equation: the number of complete response (CR) participants + the number of partial response (PR) participants + the number of stable disease (SD) participants / the number of complete response (CR) participants + the number of partial response (PR) participants + the number of stable disease (SD) participants + the number of progressive disease (PD) participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR/Clinical Response) | Up to 6 months | Using RECIST v1.1 criteria, ORR was determined by following equation: the number of partial response (PR) participants / the number of partial response (PR) participants + the number of stable disease (SD) participants + the number of progressive disease (PD) participants. |
| Progression-free Survival (PFS) | Up to 24 months (after the first patient is accrued) | Progression-free survival is defined as the time from the start of treatment until first evidence of disease progression, death, or date of last contact. The (median) length of time that subjects with previously-treated advanced NSCLC, who were treated with the combination of AMG 102 and erlotinib, are both alive and free of disease progression as estimated by the Kaplan-Meier method. For participants not known to have died as of the data cut-off date and who did not have PD, the PFS date was censored at the last contact date (contacts considered in the determination of last progression free disease assessment). |
| Overall Survival (OS) | Up to 24 months (after the first evaluable patient is accrued) | Overall Survival was computed for all participants and is defined as the time between start of treatment and death. The (median) length of time in months that subjects with previously-treated advanced NSCLC, treated with the combination of AMG 102 and erlotinib, remain alive estimated by the Kaplan-Meier method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AMG 102 + Erlotinib | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase II AMG 102 + Erlotinib | Death | 1 |
| Phase II AMG 102 + Erlotinib | Physician Decision | 2 |
| Phase II AMG 102 + Erlotinib | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | AMG 102 + Erlotinib |
|---|---|
| Age, Continuous | 65 years |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 45 / 45 |
| serious Total, serious adverse events | 18 / 45 |
Outcome results
Primary
Disease Control Rate (DCR)
Using RECIST v1.1 criteria, DCR was determined by following equation: the number of complete response (CR) participants + the number of partial response (PR) participants + the number of stable disease (SD) participants / the number of complete response (CR) participants + the number of partial response (PR) participants + the number of stable disease (SD) participants + the number of progressive disease (PD) participants.
Time frame: Six weeks from initiation of treatment with AMG 102 + Erlotinib
Population: All patients who who received at least one dose of AMG 102 and had post-treatment imaging studies for response evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria at six weeks (RESPONSE EVALUABLE)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMG 102 + Erlotinib | Disease Control Rate (DCR) | 60 percentage of patients |
Primary
Percentage of Participants That Experienced a Dose Limiting Toxicity
Determination of the safety and recommended phase II dose of AMG 102 when combined with erlotinib for the treatment of patients with advanced, previously-treated NSCLC.
Time frame: During first cycle of treatment (3 weeks)
Population: In the absence of DLTs among the first 7 pts treated, AMG 102 + Erlotinib (150 mg) daily (3 weeks) was declared the RP2D.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMG 102 + Erlotinib | Percentage of Participants That Experienced a Dose Limiting Toxicity | 0 percentage of participants |
Secondary
Objective Response Rate (ORR/Clinical Response)
Using RECIST v1.1 criteria, ORR was determined by following equation: the number of partial response (PR) participants / the number of partial response (PR) participants + the number of stable disease (SD) participants + the number of progressive disease (PD) participants.
Time frame: Up to 6 months
Population: All patients who who received at least one dose of AMG 102 and had post-treatment imaging studies for response evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria at six weeks (RESPONSE EVALUABLE)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMG 102 + Erlotinib | Objective Response Rate (ORR/Clinical Response) | 8.8 percentage of patients |
Secondary
Overall Survival (OS)
Overall Survival was computed for all participants and is defined as the time between start of treatment and death. The (median) length of time in months that subjects with previously-treated advanced NSCLC, treated with the combination of AMG 102 and erlotinib, remain alive estimated by the Kaplan-Meier method.
Time frame: Up to 24 months (after the first evaluable patient is accrued)
Population: All patients who who received at least one dose of AMG 102 and had post-treatment imaging studies for response evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria at six weeks (RESPONSE EVALUABLE)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMG 102 + Erlotinib | Overall Survival (OS) | 6.6 months |
Secondary
Progression-free Survival (PFS)
Progression-free survival is defined as the time from the start of treatment until first evidence of disease progression, death, or date of last contact. The (median) length of time that subjects with previously-treated advanced NSCLC, who were treated with the combination of AMG 102 and erlotinib, are both alive and free of disease progression as estimated by the Kaplan-Meier method. For participants not known to have died as of the data cut-off date and who did not have PD, the PFS date was censored at the last contact date (contacts considered in the determination of last progression free disease assessment).
Time frame: Up to 24 months (after the first patient is accrued)
Population: All patients who who received at least one dose of AMG 102 and had post-treatment imaging studies for response evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria at six weeks (RESPONSE EVALUABLE)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMG 102 + Erlotinib | Progression-free Survival (PFS) | 2.6 months |