Neoplasms
Conditions
Keywords
Antibodies, neoplasm
Brief summary
This is a Phase 1B/2, non-randomized, dose-escalation, multicenter, open-label study designed to evaluate the safety and tolerability of robatumumab (SCH 717454, MK-7454) in combination with standard treatment in participants with advanced solid tumors to be conducted in conformance with Good Clinical Practices. Six different treatment regimens will be investigated in combination with robatumumab. The study will be divided into two parts. Part 1 will consist of initial safety evaluation and dose-finding of robatumumab in combination with each treatment regimen. Part 2 will consist of an expansion of each robatumumab regimen at a newly established dose level, to better define safety, tolerability, and initial efficacy in specific target populations.
Interventions
DRUGCarboplatin
DRUGEpirubicin
BIOLOGICALTrastuzumab
DRUGEverolimus
DRUGGemcitabine
BIOLOGICALRobatumumab
In Part 1, robatumumab was to be administered at 10 mg/kg, 15 mg/kg (for Regimens B and C), or 20 mg/kg together with the assigned standard treatment. For Part 2, robatumumab was to be administered at the dose selected during Part 1, based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK) and pharmacodynamic (PD) data.
BIOLOGICALCetuximab
DRUGPaclitaxel
DRUGCisplatin
DRUG5-FU
DRUGErlotinib
DRUGIrinotecan
DRUGFolinic Acid
Sponsors
Merck Sharp & Dohme LLC
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
* Be willing and able to provide written informed consent for the study. * Be ±18 years of age of either sex and of any race/ethnicity; * Part 1: Have a histologically or cytologically confirmed advanced malignant solid tumor; * Part 2: Have a histologically or cytologically confirmed, with measurable disease (as defined by Response Evaluation Criteria in Solid Tumors \[RECIST\]), advanced, malignant solid tumor. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of \<=2. * Have adequate organ function within 3 weeks prior to first study drug administration.
Exclusion criteria
* Not have known treated or untreated leptomeningeal metastasis or a metastatic central nervous system lesion. * Not have a history of another malignancy * Not have received prior therapy with any anti-insulin-like growth factor receptor 1 (anti-IGF-1R) monoclonal antibody. * Not have received radiation therapy within 2 weeks prior to first study drug administration. * Not have received radiation therapy to \>25% of his/her total bone marrow during his/her lifetime. * Not have undergone major surgery within 3 weeks prior to first study drug administration. * Not have known human immunodeficiency virus (HIV) infection or a known HIV-related malignancy. * Not have known active hepatitis B or C. * Not have any serious or uncontrolled infection. * Not have uncontrolled diabetes mellitus. * Not have had any of the following within 6 months prior to first study drug administration: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality, cerebrovascular accident or transient ischemic attack, or seizure disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Up to ~30 days after the final dose of robatumumab (Up to ~14 months) | Overall best response was determined by RECIST criteria. Types of overall response could be: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Assessable (NA) or Incomplete Response/Stable Disease (IR/SD). |
| Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs) | Up to ~30 days after the final dose of robatumumab (Up to ~14 months) | An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to this study drug. AEs may include the onset of new illness and the exacerbation of pre-existing conditions. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Regimen A: FOLFIRI (± Cetuximab) + Robatumumab Participants with colorectal adenocarcinoma receive FOLFIRI (Irinotecan 180 mg/m\^2+ folinic acid 400 mg/m\^2+ 5-FU 400 mg/m\^2 bolus followed by 2400 mg/m\^2 IV infusion over 46 hours) (± cetuximab initial dose of 400 mg/m\^2 IV followed by once-weekly doses of 250 mg/m\^2 IV) PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 2-week cycle. | 2 |
| Regimen B: Carboplatin + Paclitaxel + Robatumumab Participants with non-small cell lung cancer receive carboplatin administered at an AUC of 6 mg/mL/min IV PLUS paclitaxel 225 mg/m\^2 IV PLUS robatumumab 15 mg/kg IV on Day 1 of each 3-week cycle. | 3 |
| Regimen C: Epirubicin + Cisplatin + 5-FU + Robatumumab Participants with gastric adenocarcinoma receive epirubicin 50 mg/m\^2 IV PLUS cisplatin 60 mg/m\^2 IV PLUS 5-FU 200 mg/m\^2/day administered via a 21-week continuous IV infusion PLUS robatumumab 15 mg/kg IV on Day 1 of each 3-week cycle. | 0 |
| Regimen D: Trastuzumab + Robatumumab Participants with Her2+ breast cancer receive trastuzumab 4 mg/kg IV once every week PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle. | 2 |
| Regimen E: mTor Inhibitor (Everolimus) + Robatumumab Participants with renal cell cancer receive mTor inhibitor (everolimus) 10 mg orally once per day PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle. | 4 |
| Regimen F: Gemcitabine (± Erlotinib) + Robatumumab Participants with pancreatic adenocarcinoma receive gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 in Cycle 1 and on Days 1, 8 and 15 in subsequent cycles (± erlotinib 100 mg per day orally) PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle. (Cycle 1 is 8 weeks.) | 4 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Progression of Disease | 2 | 1 | 0 | 1 | 1 | 1 |
| Overall Study | Symptomatic Deterioration | 0 | 1 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Regimen A: FOLFIRI (± Cetuximab) + Robatumumab | Regimen B: Carboplatin + Paclitaxel + Robatumumab | Regimen D: Trastuzumab + Robatumumab | Regimen E: mTor Inhibitor (Everolimus) + Robatumumab | Regimen F: Gemcitabine (± Erlotinib) + Robatumumab | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 47.0 Years STANDARD_DEVIATION 2.8 | 54.0 Years STANDARD_DEVIATION 4.4 | 48.0 Years STANDARD_DEVIATION 2.8 | 53.3 Years STANDARD_DEVIATION 13.5 | 70.8 Years STANDARD_DEVIATION 3 | 56.5 Years STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 4 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 3 / 3 | 2 / 2 | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 0 / 2 | 2 / 3 | 1 / 2 | 2 / 4 | 2 / 4 |
Outcome results
Primary
Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to this study drug. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
Time frame: Up to ~30 days after the final dose of robatumumab (Up to ~14 months)
Population: The All Treated Set (safety) consisted of all participants who received ≥1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regimen A: FOLFIRI (± Cetuximab) + Robatumumab | Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs) | 2 Participants |
| Regimen B: Carboplatin + Paclitaxel + Robatumumab | Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs) | 3 Participants |
| Regimen D: Trastuzumab + Robatumumab | Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs) | 2 Participants |
| Regimen E: mTor Inhibitor (Everolimus) + Robatumumab | Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs) | 4 Participants |
| Regimen F: Gemcitabine (± Erlotinib) + Robatumumab | Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs) | 4 Participants |
Primary
Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response
Overall best response was determined by RECIST criteria. Types of overall response could be: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Assessable (NA) or Incomplete Response/Stable Disease (IR/SD).
Time frame: Up to ~30 days after the final dose of robatumumab (Up to ~14 months)
Population: The All Treated Set (efficacy) consisted of all participants who received ≥1 dose of study drug and were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regimen A: FOLFIRI (± Cetuximab) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Complete Response (CR) | 0 Participants |
| Regimen A: FOLFIRI (± Cetuximab) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Partial Response (PR) | 0 Participants |
| Regimen A: FOLFIRI (± Cetuximab) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Stable Disease (SD) | 0 Participants |
| Regimen A: FOLFIRI (± Cetuximab) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Progressive Disease (PD) | 2 Participants |
| Regimen A: FOLFIRI (± Cetuximab) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Not Assessable (NA) | 0 Participants |
| Regimen A: FOLFIRI (± Cetuximab) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Incomplete Response/Stable Disease (IR/SD) | 0 Participants |
| Regimen B: Carboplatin + Paclitaxel + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Not Assessable (NA) | 0 Participants |
| Regimen B: Carboplatin + Paclitaxel + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Incomplete Response/Stable Disease (IR/SD) | 0 Participants |
| Regimen B: Carboplatin + Paclitaxel + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Complete Response (CR) | 0 Participants |
| Regimen B: Carboplatin + Paclitaxel + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Stable Disease (SD) | 2 Participants |
| Regimen B: Carboplatin + Paclitaxel + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Progressive Disease (PD) | 1 Participants |
| Regimen B: Carboplatin + Paclitaxel + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Partial Response (PR) | 0 Participants |
| Regimen D: Trastuzumab + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Progressive Disease (PD) | 1 Participants |
| Regimen D: Trastuzumab + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Not Assessable (NA) | 0 Participants |
| Regimen D: Trastuzumab + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Complete Response (CR) | 0 Participants |
| Regimen D: Trastuzumab + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Stable Disease (SD) | 1 Participants |
| Regimen D: Trastuzumab + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Partial Response (PR) | 0 Participants |
| Regimen D: Trastuzumab + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Incomplete Response/Stable Disease (IR/SD) | 0 Participants |
| Regimen E: mTor Inhibitor (Everolimus) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Progressive Disease (PD) | 1 Participants |
| Regimen E: mTor Inhibitor (Everolimus) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Partial Response (PR) | 0 Participants |
| Regimen E: mTor Inhibitor (Everolimus) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Stable Disease (SD) | 2 Participants |
| Regimen E: mTor Inhibitor (Everolimus) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Incomplete Response/Stable Disease (IR/SD) | 0 Participants |
| Regimen E: mTor Inhibitor (Everolimus) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Not Assessable (NA) | 0 Participants |
| Regimen E: mTor Inhibitor (Everolimus) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Complete Response (CR) | 0 Participants |
| Regimen F: Gemcitabine (± Erlotinib) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Not Assessable (NA) | 0 Participants |
| Regimen F: Gemcitabine (± Erlotinib) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Stable Disease (SD) | 1 Participants |
| Regimen F: Gemcitabine (± Erlotinib) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Partial Response (PR) | 0 Participants |
| Regimen F: Gemcitabine (± Erlotinib) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Incomplete Response/Stable Disease (IR/SD) | 0 Participants |
| Regimen F: Gemcitabine (± Erlotinib) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Progressive Disease (PD) | 1 Participants |
| Regimen F: Gemcitabine (± Erlotinib) + Robatumumab | Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | Complete Response (CR) | 0 Participants |