Lung Cancer, Small Cell Lung Cancer, Solid Tumors, Extensive-stage Small Cell Lung Cancer
Conditions
Keywords
Extensive disease, Extrathoracic metasasis, Malignant pericardial effusion, Malignant pleural effusion, Contralateral hilar adenopathy
Brief summary
This trial is titled A Phase 1b/2 trial of AMG 479 or AMG 102 with Platinum-Based Chemotherapy as First-Line Treatment for Extensive Stage Small-Cell Lung Cancer (SCLC). Part 1, the phase 1b portion of this study, is a multicenter, open-label investigation to identify safe dose levels of either AMG 102 or AMG 479 in combination with etoposide plus cisplatin or carboplatin in subjects with previously untreated extensive stage SCLC. Part 2, the phase 2 portion of this study, is a multicenter, double-blind, 3-arm investigation to evaluate overall survival of either AMG 102 or AMG 479 in combination with platinum-based chemotherapy.
Interventions
DRUGAMG 479
AMG 479 is administered to subjects
DRUGEtoposide
Etoposide is administered to subjects
DRUGPlacebo
Placebo is administered with Carboplatin and Etoposide
DRUGAMG 102
AMG 102 is administered to subjects
DRUGCarboplatin
Carboplatin is administered to some subjects in combination
DRUGCisplatin
Cisplatin is administered to some subjects in combination
Sponsors
NantCell, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Histologically or cytologically confirmed SCLC * Extensive disease, defined by at least one of the following: * No limited disease (ie, no disease confined to the ipsilateral hemithorax, which can be safely encompassed within a tolerable radiation field) * Extrathoracic metastases * Malignant pericardial or pleural effusion * Contralateral hilar adenopathy * Measurable or nonmeasurable disease, as defined by modified RECIST * Eastern Cooperative Oncology Group (ECOG) status 0 or 1 * ≥18 years old * Life expectancy (with therapy) ≥3 months * Adequate hematologic, hepatic, coagulation, renal, and metabolic function * Diabetes, if present, must be controlled, with glycosylated hemoglobin (HbA1C) ≤ 8% and fasting glucose levels ≤160 mg/dL Key
Exclusion criteria
* Prior chemotherapy, chemoradiation, or investigational agent for SCLC * Prior radiotherapy to \>25% of the bone marrow * Symptomatic or untreated central nervous system metastases (with exceptions) * Currently or previously treated with biologic, immunologic or other therapies for SCLC * Current serious or nonhealing wound or ulcer * History of prior concurrent other malignancy (with exceptions) * Thorombosis or vascular ischemic events within the last 12 months such as DVT, PE, TIA or MI * Any clinically significant medical condition other than cancer (eg, cardiovascular disease or COPD), which could interfere with the safe delivery of study treatment or risk of toxicity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in Ganitumab Treated Subjects -Phase 2 | Time from randomization to death from any cause, approximately 14 months | The primary efficacy endpoint was overall survival, defined as time from randomization to death from any cause |
| Overall Survival in Rilotumumab Treated Subjects-Phase 2 | Time from randomization to death from any cause, approximately 14 months | The primary efficacy endpoint is overall survival, defined as time from randomization to death from any cause |
| Number of Subjects With Dose Limiting Toxicities-Phase 1 | First 21 days after start of study treatment | For Part 1, DLTs were defined as the incidence during the first 21 days of starting study treatment of any Grade 3 or higher hematologic or non-hematologic toxicity related to AMG 479 or AMG 102, or the combination of AMG 479 or AMG 102 with chemotherapy, except for lymphocytopenia and anemia. DLTs did not include fatigue, nausea, diarrhea, vomiting, hyperglycemia, neutropenia, thrombocytopenia, increased AST or ALT, or pulmonary embolism unless specific criteria were met as stated in protocol section 6.1.3.2. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: AMG 479/Carboplatin+Etoposide AMG 479 in combination with etoposide plus carboplatin (Cohort 1) | 6 |
| Phase 1: AMG 479/Cisplatin+Etoposide cisplatin (Cohort 2) | 8 |
| Phase 1: AMG102/Carboplatin+Etoposide AMG 102 in combination with etoposide plus carboplatin (Cohort 3) | 6 |
| Phase 1: AMG 102/Cisplatin+Etoposide cisplatin (Cohort 4) | 8 |
| Phase 2 Ganitumab Blinded AMG 479 study drug and carboplatin or cisplatin and etoposide | 62 |
| Phase 2 Rilotumumab Blinded AMG 102 study drug and carboplatin or cisplatin and etoposide | 62 |
| Phase 2 Placebo Blinded placebo and carboplatin or cisplatin and etoposide | 61 |
| Total | 213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 2 | 0 | 1 |
| Overall Study | Death | 5 | 4 | 4 | 7 | 54 | 54 | 52 |
| Overall Study | Full Consent withdrawn | 1 | 3 | 0 | 0 | 1 | 3 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 2 | 0 | 4 |
| Overall Study | Noncompliance | 0 | 1 | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Other event | 0 | 0 | 2 | 0 | 2 | 4 | 2 |
Baseline characteristics
| Characteristic | Phase 1: AMG 479/Carboplatin+Etoposide | Total | Phase 2 Placebo | Phase 2 Rilotumumab | Phase 2 Ganitumab | Phase 1: AMG 102/Cisplatin+Etoposide | Phase 1: AMG102/Carboplatin+Etoposide | Phase 1: AMG 479/Cisplatin+Etoposide |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 7.3 | 60.1 years STANDARD_DEVIATION 8.3 | 59.6 years STANDARD_DEVIATION 9.7 | 60.8 years STANDARD_DEVIATION 7.6 | 59.8 years STANDARD_DEVIATION 7.6 | 59.4 years STANDARD_DEVIATION 5 | 60.7 years STANDARD_DEVIATION 8 | 55.4 years STANDARD_DEVIATION 9 |
| Histologically or cytologically confirmed SCLC | 6 Participants | 212 Participants | 61 Participants | 62 Participants | 62 Participants | 8 Participants | 6 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 38 Participants | 6 Participants | 13 Participants | 13 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 174 Participants | 55 Participants | 49 Participants | 48 Participants | 7 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Female | 4 Participants | 54 Participants | 14 Participants | 15 Participants | 14 Participants | 2 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 159 Participants | 47 Participants | 47 Participants | 48 Participants | 6 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 6 | 4 / 8 | 4 / 6 | 7 / 8 | 54 / 62 | 54 / 62 | 52 / 61 |
| other Total, other adverse events | 6 / 6 | 6 / 7 | 6 / 6 | 8 / 8 | 58 / 59 | 61 / 61 | 57 / 59 |
| serious Total, serious adverse events | 5 / 6 | 2 / 7 | 4 / 6 | 7 / 8 | 7 / 59 | 6 / 61 | 3 / 59 |
Outcome results
Primary
Number of Subjects With Dose Limiting Toxicities-Phase 1
For Part 1, DLTs were defined as the incidence during the first 21 days of starting study treatment of any Grade 3 or higher hematologic or non-hematologic toxicity related to AMG 479 or AMG 102, or the combination of AMG 479 or AMG 102 with chemotherapy, except for lymphocytopenia and anemia. DLTs did not include fatigue, nausea, diarrhea, vomiting, hyperglycemia, neutropenia, thrombocytopenia, increased AST or ALT, or pulmonary embolism unless specific criteria were met as stated in protocol section 6.1.3.2.
Time frame: First 21 days after start of study treatment
Population: This endpoint is for phase 1 subjects only
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 2 Ganitumab | Number of Subjects With Dose Limiting Toxicities-Phase 1 | 1 Participants |
| Phase 2 Placebo | Number of Subjects With Dose Limiting Toxicities-Phase 1 | 0 Participants |
| Phase 1: AMG102/Carboplatin+Etoposide | Number of Subjects With Dose Limiting Toxicities-Phase 1 | 0 Participants |
| Phase 1: AMG 102/Cisplatin+Etoposide | Number of Subjects With Dose Limiting Toxicities-Phase 1 | 0 Participants |
| Phase 2 Rilotumumab | Number of Subjects With Dose Limiting Toxicities-Phase 1 | 0 Participants |
| Phase 2 Placebo | Number of Subjects With Dose Limiting Toxicities-Phase 1 | 0 Participants |
| Phase 2 Placebo | Number of Subjects With Dose Limiting Toxicities-Phase 1 | 0 Participants |
Primary
Overall Survival in Ganitumab Treated Subjects -Phase 2
The primary efficacy endpoint was overall survival, defined as time from randomization to death from any cause
Time frame: Time from randomization to death from any cause, approximately 14 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2 Ganitumab | Overall Survival in Ganitumab Treated Subjects -Phase 2 | 10.7 months |
| Phase 2 Placebo | Overall Survival in Ganitumab Treated Subjects -Phase 2 | 10.8 months |
Primary
Overall Survival in Rilotumumab Treated Subjects-Phase 2
The primary efficacy endpoint is overall survival, defined as time from randomization to death from any cause
Time frame: Time from randomization to death from any cause, approximately 14 months
Population: This endpoint was phase 2 subjects only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2 Rilotumumab | Overall Survival in Rilotumumab Treated Subjects-Phase 2 | 12.2 months |
| Phase 2 Placebo | Overall Survival in Rilotumumab Treated Subjects-Phase 2 | 10.8 months |