Advanced Squamous Non-Small Cell Lung Cancer
Conditions
Keywords
AMG 479, IGF-1R, Apoptosis, Monoclonal Antibody, Advanced Squamous Non-Small Cell Lung Cancer, antibody 1st-line
Brief summary
This is a global, multicenter, 2-part, open-label phase 1b and single-arm phase 2 study designed to evaluate the safety and efficacy of AMG 479 in combination with paclitaxel and carboplatin for the first-line treatment of advanced squamous non-small cell lung carcinoma.
Interventions
BIOLOGICALAMG 479
AMG 479 at 12 mg/kg IV in combination with chemotherapy Day 1 of cycle 1 to 6 (except for subjects being evaluated by intensive PK who will be administered AMG 479 on day 2 of cycle 1 and then day 1 of every cycle thereafter) followed by AMG 479 at 12 mg/kg IV monotherapy for up to 24 months from study day 1
DRUGCarboplatin
Carboplatin (AUC 6) IV infusion over 30 (± 10) minutes according to institutional guidelines Day 1 of Cycle 1 to 6
DRUGPaclitaxel
Paclitaxel at 200 mg/m2 IV infusion over 3 hours (± 30 minutes) according to institutional guidelines Day 1 of Cycle 1 to 6
Sponsors
NantCell, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed advanced squamous NSCLC * Measurable disease as defined per modified RECIST criteria * ECOG performance status of 0 or 1 * ≥18 years old * Adequate glycemic function, for subjects with known diabetes
Exclusion criteria
* Untreated or symptomatic central nervous system (CNS) metastases * Prior anti-cancer therapy as follows: Any prior chemotherapy for squamous NSCLC; Any prior adjuvant or neoadjuvant chemotherapy for squamous NSCLC; Any prior chemoradiation for squamous NSCLC; Central (chest) radiation therapy ≤ 28 days prior to enrollment, radiation therapy for peripheral lesions≤14 days prior to enrollment for squamous NSCLC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Dose Limiting Toxicities | Part 1 only up to 21 days | DLTs were defined as grade 3 or higher hematological or nonhematological toxicities that, in the opinion of the investigator, were related to ganitumab or the combination of ganitumab and paclitaxel or carboplatin during this period. These did not include fatigue, nausea, diarrhea, vomiting, hyperglycemia, neutropenia, thrombocytopenia, anemia, lymphopenia, alopecia, increased ALT or AST, or pulmonary embolism unless they met certain criteria. |
| Part 2: Objective Response Rate | From start of treatment up to approximately 16 months | Part 2: Objective Response Rate as per modified RECIST criteria by investigator review Objective response was defined as a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors \[RECIST\] and was determined only for subjects with measurable disease at baseline. Per RECIST: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 30 days after last dose, up to 5 months | Adverse events were assessed using CTCAE v 3.0 |
| Number of Participants With Anti-AMG 479 Antibody Formation | From start of treatment up to approximately 16 months | — |
| Progression Free Survival | From start of treatment up to approximately 16 months | PFS was defined as the time from study day 1 to the first observation of disease progression per investigator review (as classified by modified RECIST or death due to any cause, or censoring. Disease progression per RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression. |
| Time to Progression and Duration of Response | From start of treatment up to approximately 16 months | Time to Progression (TTP) is defined as the time from Day 1 to the first observation of disease progression (per modified RECIST). Disease progression per RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression. DOR was the time from the first observation of an objective response to the subsequent time of disease progression (per modified RECIST or clinical progression, whichever came first) or death due to any cause. Objective response = a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors \[RECIST\]. Per RECIST: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Countries
United States
Participant flow
Pre-assignment details
Primary for discontinuing study 1 subject documented completed taken from end-of-study page of the CRF site entered (end of study defined all subjects that completed 60-day follow-up visit, death, 26 months post final subject randomization, whichever earlier). Based on the date of subject's end-of-study visit, primary reason likely the subject discontinued study to sponsor's early closing of the study. Part 1 and 2 were analyzed together because the same dose was given in both parts.
Participants by arm
| Arm | Count |
|---|---|
| Ganitumab 18 mg/kg + Paclitaxel/Carboplatin AMG 479 at 18 mg/kg in combination with paclitaxel/carboplatin for 4 to 6 cycles followed by AMG 479 at 18 mg/kg monotherapy for 24 months from study day 1
AMG 479: AMG 479 at 18mg/kg IV in combination with chemotherapy Day 1 of cycle 1 to 6 (except for subjects being evaluated by intensive PK who will be administered AMG 479 on Day 2 of cycle 1 and then day 1 of every cycle thereafter) followed by AMG 479 at 18 mg/kg IV monotherapy for up to 24 months from day 1
Carboplatin: Carboplatin (AUC 6) IV infusion over 30 (± 10) minutes according to institutional guidelines Day 1 of Cycle 1 to 6
Paclitaxel: Paclitaxel at 200 mg/m2 IV infusion over 3 hours (± 30 minutes) according to institutional guidelines Day 1 of Cycle 1 to 6 | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 8 |
| Overall Study | Study early termination | 5 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Ganitumab 18 mg/kg + Paclitaxel/Carboplatin |
|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 9.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 15 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 15 |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 7 / 14 |
Outcome results
Primary
Part 1: Number of Dose Limiting Toxicities
DLTs were defined as grade 3 or higher hematological or nonhematological toxicities that, in the opinion of the investigator, were related to ganitumab or the combination of ganitumab and paclitaxel or carboplatin during this period. These did not include fatigue, nausea, diarrhea, vomiting, hyperglycemia, neutropenia, thrombocytopenia, anemia, lymphopenia, alopecia, increased ALT or AST, or pulmonary embolism unless they met certain criteria.
Time frame: Part 1 only up to 21 days
Population: Dose-limiting-toxicity-evaluable subjects were defined as those who had received 1 dose of ganitumab in combination with paclitaxel and carboplatin and had completed 1 cycle (21 days) of study treatment or experienced a DLT related to ganitumab or the combination of ganitumab and paclitaxel/carboplatin during the first cycle (21 days) of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AMG 479 18 mg/kg + Paclitaxel/Carboplatin | Part 1: Number of Dose Limiting Toxicities | 0 Participants |
Primary
Part 2: Objective Response Rate
Part 2: Objective Response Rate as per modified RECIST criteria by investigator review Objective response was defined as a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors \[RECIST\] and was determined only for subjects with measurable disease at baseline. Per RECIST: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From start of treatment up to approximately 16 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMG 479 18 mg/kg + Paclitaxel/Carboplatin | Part 2: Objective Response Rate | 27 percentage of participants |
Secondary
Number of Participants With Adverse Events
Adverse events were assessed using CTCAE v 3.0
Time frame: 30 days after last dose, up to 5 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AMG 479 18 mg/kg + Paclitaxel/Carboplatin | Number of Participants With Adverse Events | 14 Participants |
Secondary
Number of Participants With Anti-AMG 479 Antibody Formation
Time frame: From start of treatment up to approximately 16 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AMG 479 18 mg/kg + Paclitaxel/Carboplatin | Number of Participants With Anti-AMG 479 Antibody Formation | Total binding antibody incidence | 3 Participants |
| AMG 479 18 mg/kg + Paclitaxel/Carboplatin | Number of Participants With Anti-AMG 479 Antibody Formation | neutralizing antibody incidence | 0 Participants |
Secondary
Progression Free Survival
PFS was defined as the time from study day 1 to the first observation of disease progression per investigator review (as classified by modified RECIST or death due to any cause, or censoring. Disease progression per RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.
Time frame: From start of treatment up to approximately 16 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMG 479 18 mg/kg + Paclitaxel/Carboplatin | Progression Free Survival | 20.0 weeks |
Secondary
Time to Progression and Duration of Response
Time to Progression (TTP) is defined as the time from Day 1 to the first observation of disease progression (per modified RECIST). Disease progression per RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression. DOR was the time from the first observation of an objective response to the subsequent time of disease progression (per modified RECIST or clinical progression, whichever came first) or death due to any cause. Objective response = a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors \[RECIST\]. Per RECIST: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From start of treatment up to approximately 16 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| AMG 479 18 mg/kg + Paclitaxel/Carboplatin | Time to Progression and Duration of Response | Time to Progression | NA Weeks |
| AMG 479 18 mg/kg + Paclitaxel/Carboplatin | Time to Progression and Duration of Response | Duration of Response | NA Weeks |