Non-Small Cell Lung Cancer
Conditions
Keywords
MK-3475, Pembrolizumab, Carboplatin, Nab-paclitaxel
Brief summary
This is a phase I/II study for previously untreated subjects with advanced NSCLC. The study will take place in two phases. First, a cohort of twelve participants will be enrolled in phase I part and will be treated with carboplatin, nab-paclitaxel and pembrolizumab. A cohort of twelve subjects will be evaluated for safety and tolerability after 2 cycles of therapy. All subjects who receive either nab-paclitaxel or pembrolizumab will be evaluable. If 33% of subjects or less have unacceptable toxicity in the first cohort or any subsequent cohort (if necessary), the study will proceed to the Phase II part. If more than 33% have unacceptable toxicity, 12 additional subjects will be enrolled in a second cohort, if necessary. If unacceptable toxicity is seen in more than 33% in Cohort 2, the study will end due to unacceptable toxicity of this drug combination. The phase II part of the study is a single arm study. All subjects will be treated with carboplatin, nab-paclitaxel, and pembrolizumab in 21-day cycles for up to 4 cycles. Mandatory pre-treatment tumor biopsies will be obtained prior to initiating treatment for all subjects (only if adequate archived samples are unavailable). Mandatory tumor biopsies will be obtained in the Phase II part of the study after 4 cycles of study treatment or at the time of progression, whichever comes first. For subjects without progression of disease after Cycle 4, pembrolizumab will continue every 3 weeks for up to 2 years or until unacceptable toxicity.
Detailed description
OUTLINE: This is a multi-center study. INVESTIGATIONAL TREATMENT: Phase I, Cohort 1 Induction Therapy: * Carboplatin AUC 6 IV, Day 1 * Nab-paclitaxel 100 mg/m\^2 IV, Days 1, 8, 15 * pembrolizumab 2 mg/kg IV, Day 1 * Cycle length: 21 days; number of cycles: 4 Phase I, Cohort 1 Maintenance Therapy: For subjects who have confirmed CR, PR, or SD (non-progression) after 4 cycles of induction therapy, maintenance therapy with pembrolizumab 2\* mg/kg will continue on Day 1 of each 21-day cycle. Treatment will continue until progression of disease, unacceptable toxicity, or for a maximum of 2 years from Cycle 1, Day 1 (C1D1). Subjects who complete 24 months of treatment with pembrolizumab may be eligible for up to one year of additional study treatment if they progress after stopping study treatment provided they continue to meet inclusion criteria requirements. If unacceptable toxicity is seen in Phase I, Cohort 1, 12 additional participants will be enrolled. Phase I, Cohort 2 Induction Therapy (if necessary): * Carboplatin AUC 6 IV, Day 1 * Nab-paclitaxel 100 mg/m\^2 IV, Days 1, 8, 15 * pembrolizumab 2 mg/kg IV, Day 1 (cycle 2-4 only) * Cycle length: 21 days; Number of cycles: 4 Phase I, Cohort 2 Maintenance Therapy: For subjects who have confirmed CR, PR, or SD (non-progression) after 4 cycles of induction therapy, maintenance therapy with pembrolizumab 2\* mg/kg will continue on Day 1 of each 21-day cycle. Treatment will continue until progression of disease, unacceptable toxicity, or for a maximum of 2 years from Cycle 2, Day 1 (C2D1). Subjects who complete 24 months of treatment with pembrolizumab may be eligible for up to one year of additional study treatment if they progress after stopping study treatment provided they continue to meet inclusion criteria requirements. Phase II Induction Therapy: * Carboplatin AUC 6 IV, Day 1 * Nab-paclitaxel 100 mg/m\^2 IV, Days 1, 8, 15 * pembrolizumab 200mg IV, Day 1 of each cycle * Cycle length: 21 days; number of cycles: 4 Phase II Maintenance Therapy: For subjects who have confirmed CR, PR, or SD (non-progression) after 4 cycles of induction therapy, maintenance therapy with pembrolizumab 200 mg will continue on Day 1 of each 21-day cycle. Treatment will continue until progression of disease, unacceptable toxicity, or for a maximum of 2 years from Cycle 1, Day 1 (C1D1). Subjects who complete 24 months of treatment with pembrolizumab may be eligible for up to one year of additional study treatment if they progress after stopping study treatment provided they meet the requirements. \*As additional data from ongoing trials becomes available, the dose of pembrolizumab may be adjusted.
Interventions
DRUGCarboplatin
Carboplatin AUC 6 IV, D1 for 4 cycles (cycle = 21 days)
DRUGNab-paclitaxel
Nab-paclitaxel 100 mg/m2 IV, D1, D8, D15 for 4 cycles (cycle = 21 days)
DRUGMK-3475 (Phase I)
MK-3475 2 mg/kg IV, D1 for 4 cycles (Cohort 1) or 3 cycles (Cohort 2) (cycle = 21 days) Maintenance MK-3475 2 mg/kg IV continues every 21 days after Cycle 4 for up to 2 years.
DRUGMK-3475 (Phase II)
MK-3475 200 mg IV Day 1 of each cycle (cycle = 21 days) Maintenance MK-3475 2 mg/kg IV continues every 21 days after Cycle 4 for up to 2 years.
Sponsors
Hoosier Cancer Research Network
Merck Sharp & Dohme LLC
Celgene Corporation
Nisha Mohindra, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be willing and able to provide written informed consent for the trial and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. * Subjects must be ≥ 18 years of age. * Individuals with stage IIIB or IV, unresectable non-small cell lung cancer (NSCLC) who have not received prior chemotherapy for Stage IIIB or IV disease, and who are not candidates for curative surgery or radiation therapy. * ECOG performance status (PS) 0-1 * Measurable disease by RECIST v1.1 criteria * Prior to registration, all subjects must have archival tissue available. For subjects who have no archival tissue, but have PD-L1 testing results using the Dako 22C3 antibody, subjects will be permitted to enroll without submitting tissue. If the patient has not had prior testing and no acceptable archival tissue is available, subjects must be willing to consent to providing a pre-treatment biopsy for PD-L1 testing. Regardless of PD-L1 testing status, archival tissue will be requested for research testing if available. * Phase II subjects must be willing to consent to providing a mandatory post-treatment core biopsy for research if clinical feasible. * Women are eligible to participate if they are of non-childbearing potential or have documentation of a negative pregnancy test (serum or urine β-hCG) within 3 days of registration. Sexually active pre-menopausal women of childbearing potential must agree to use adequate, highly effective contraceptive measures, starting with the first dose of study drug and for 120 days after the last dose of last study drug. Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; (b) oral, implantable, or injectable contraceptives plus one barrier method; or (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for ≥ 1 year. * Male participants should agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of last study drug.
Exclusion criteria
* Individuals with the presence of symptomatic CNS metastases requiring radiation treatment, surgery, or ongoing use of corticosteroids. * Untreated or brain metastasis causing any symptoms, such as neurologic deficits or headache. Individuals with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of study drug and any neurologic symptoms have returned to baseline and whole brain radiation or stereotactic radiosurgery completed over 4 weeks prior to registration), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study treatment. * History of solid organ or stem cell transplant requiring immunosuppressive medications. * Any prior adjuvant cytotoxic chemotherapy within 12 months of registration. Subjects who received chemotherapy for earlier stage disease more than 12 months prior to study registration are eligible for this trial. * Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). * Any radiotherapy within 2 weeks prior to registration (4 weeks for brain radiotherapy as noted above). * Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. * History of other invasive malignancy that is currently active and/or has been treated within 12 months of registration. (Notable exceptions include: basal cell carcinoma, squamous cell carcinoma of the skin, localized prostate cancer, in situ carcinomas of the cervix and breast, and superficial bladder cancers \[non-muscle-invasive\]). * Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis. * Has a history of pneumonitis that required steroids or current pneumonitis. * Pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v 4.0 criteria. * Known significant liver disease including viral, alcoholic, active hepatitis B or C, and/or cirrhosis. * Abnormal liver or renal function as defined as: bilirubin ≥ 1.5 mg/dL; AST or ALT ≥ 2.5 x the ULN; alkaline phosphatase \> 2.5 x the ULN, there is no upper limit if bone metastasis is present in the absence of liver metastasis; creatinine \> 1.5 mg/dL * Abnormal baseline hematologic or coagulation parameters as defined as: absolute neutrophil count (ANC) \<1.5 x 10\^9/L; hemoglobin \< 9.0 g/dL; platelets \< 100 x 10\^9/L; International Normalized Ratio (INR) of prothrombin time (PT) ≥ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; Activated Partial Thromboplastin Time (aPTT) ≥ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants * Has received a live vaccine within 30 days prior to the first dose of study drug. * Known activating EGFR mutation or ALK translocation * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of pembrolizumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose | Begin C1D1 and every 2 chemotherapy cycles (6 weeks) thereafter, for up to 2 years or until unacceptable toxicity. | To determine the recommended Phase II dose (RP2D) of MK-3475 and evaluate the safety and tolerability of the combination of MK-3475 with carboplatin/nab-paclitaxel for the first line treatment of phase I participants with advanced NSCLC per CTCAE v4.0 criteria by summarizing the number of adverse events experienced by subjects. |
| Phase II: Disease Assessment for Progression-Free Survival (PFS) | From date of registration to time of first documented progression or death, whichever occurs first (estimate 9 months) | To evaluate progression-free survival (PFS) for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria. PFS is defined as the duration of time from date of registration to time of progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Phase II: Objective Response Rate | From the start of treatment until progression or death up to 24 months | To evaluate objective response rate for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Overall Survival (OS) | From date of registration to date of death from any cause up to 49 months. | To evaluate overall survival rates for phase I participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC. |
| Phase II: Overall Survival (OS) | From date of registration to date of death from any cause up to 42 months. | To evaluate overall survival rates for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC. |
| Phase I: Disease Assessment for Progression-Free Survival (PFS) | From date of registration to time of first documented progression or death, whichever occurs first (estimate 9 months) | To evaluate progression-free survival (PFS) and objective response for phase I participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Phase II: Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Begin C1D1 and every 2 cycles (6 weeks) thereafter, for up to 2 years or until unacceptable toxicity. | To evaluate the safety and tolerability of the combination of MK-3475 with carboplatin/nab-paclitaxel for the first line treatment of phase II participants with advanced NSCLC per CTCAE v4.0. Safety and tolerability is defined as rates of Grade 1-5 toxicity according to CTCAE v4. |
| All Phases: Assessment of Association of PD-L1 Expression on PFS | From date of registration to time of first documented progression. (Measurable disease will be assessed after every 2 chemotherapy cycles [every 6 weeks thereafter for up to 2 years or until unacceptable toxicity]). | To evaluate the association of PD-L1 expression on PFS for all participants receiving MK-3475. PD-L1 will be categorized as positive (≥50% expression) or negative (\<50% expression) from pre-treatment and post-treatment biopsies. PFS will be summarized by PD-L1 expression. |
| Phase II: Disease Assessment for Anti-Tumor Activity | From date of registration to time of first documented progression. (Measurable disease will be assessed after every 2 chemotherapy cycles [every 6 weeks thereafter for up to 2 years or until unacceptable toxicity]). | To evaluate anti-tumor activity for phase I participants will be reported as a percentage change in the sum of the dimensions of all measurable lesions as defined by RECIST 1.1 criteria. |
| Phase I : Objective Response Rate | From the start of treatment until progression or death up to 11 months. | To evaluate objective response rate for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria. Objective response rate (ORR), is defined as the proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST). |
| Phase I: Disease Assessment for Anti-Tumor Activity | From date of registration to time of first documented progression. (Measurable disease will be assessed after every 2 chemotherapy cycles [every 6 weeks thereafter for up to 2 years or until unacceptable toxicity]). | To evaluate anti-tumor activity for phase I participants will be reported as a percentage change in the sum of the dimensions of all measurable lesions as defined by RECIST 1.1 criteria. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase I, Cohort 1 Phase I, Cohort 1: Induction Therapy
Twelve subjects will be enrolled to Cohort 1 and treated with carboplatin AUC 6 IV on Day 1, nab-paclitaxel 100 mg/m\^2 given IV on Days 1, 8, and 15, and pembrolizumab 2\* mg/kg IV on Day 1.Treatment will continue for a maximum duration of 4 cycles with cycle length of 21 days.
Phase I, Cohort 1 Maintenance Therapy:
Participants who have confirmed CR, PR, or SD (non-progression) after 4 cycles, maintenance therapy with pembrolizumab 2\* mg/kg will continue on D1 of each 21-day cycle. Treatment will continue until progression of disease, unacceptable toxicity, or a maximum of 2 years from C1D1. | 14 |
| Phase I, Cohort 2 Phase I, Cohort 2: Induction Therapy
If unacceptable toxicity is seen in Phase I, Cohort 1, 12 additional subjects will be enrolled in Phase I, Cohort 2. Subjects will be treated with carboplatin AUC 6 given IV on Day 1 and nabpaclitaxel 100 mg/m2 given IV on Days 1, 8, and 15. Pembrolizumab 2\* mg/kg IV will be given on Day 1 starting in cycle 2. Treatment will continue for a maximum duration of 4 cycles (pembrolizumab given Cycles 2 to 4 only).
Phase I, Cohort 2 Maintenance Therapy:
For subjects who have confirmed CR, PR, or SD (non-progression) after 4 cycles of induction therapy, maintenance therapy with pembrolizumab 2\* mg/kg will continue on Day 1 of each 21- day cycle. Treatment will continue until progression of disease, unacceptable toxicity, or for a maximum of 2 years from Cycle 2, Day 1. | 0 |
| Phase II Induction Therapy Cycles 1-4
Subjects will be treated with carboplatin AUC 6 given IV on Day 1, nab-paclitaxel 100 mg/m2 given IV on Days 1, 8, and 15, and pembrolizumab 200 mg IV on Day 1. Treatment will continue for a maximum duration of 4 cycles of study treatment. Each cycle starts when all the criteria to start a new cycle are met. A cycle is defined only when you can give all 3 drugs on Day 1, and it coincides with pembrolizumab. Pembrolizumab should be given with carboplatin and nab-paclitaxel on day 1 of the cycle. Chemotherapies may be withheld for six weeks, while pembrolizumab can be withheld for 12-weeks. If there is a pembrolizumab-specific toxicity requiring pembrolizumab to be held, chemotherapy should be resumed without pembrolizumab within 6 weeks if it is felt that chemotherapy is safe by the site investigator. Delays in chemotherapy beyond 6 weeks require withdrawal from the study treatment.
Maintenance Therapy
For subjects who have confirmed CR, PR, or SD (non-progression) after 4 cycles of induction therapy, maintenance therapy with pembrolizumab 200 mg will continue on Day 1 of each 21-day cycle. Treatment will continue until progression of disease, unacceptable toxicity, or for a maximum of 2 years from Cycle 1 Day 1. | 32 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Follow up | Death | 11 | 0 | 19 |
| Follow up | Patient Refused Follow-up | 1 | 0 | 0 |
| Follow up | Study Terminated | 1 | 0 | 8 |
| Follow up | Symptomatic deterioration | 1 | 0 | 1 |
| Follow up | Withdrawal by Subject | 0 | 0 | 2 |
| Study Treatment | AE/ Side Effects/ Complications | 4 | 0 | 6 |
| Study Treatment | Death | 0 | 0 | 2 |
| Study Treatment | Disease Progression | 8 | 0 | 20 |
| Study Treatment | Patient withdrawal after therapy start | 1 | 0 | 1 |
| Study Treatment | symptomatic deterioration | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Phase II | Total | Phase I, Cohort 1 |
|---|---|---|---|
| Age, Continuous | 65.5 years | 65.5 years | 66 years |
| ECOG 0 | 8 Participants | 14 Participants | 6 Participants |
| ECOG 1 | 23 Participants | 31 Participants | 8 Participants |
| ECOG Missing | 1 Participants | 1 Participants | 0 Participants |
| Histology Subtype Adenocarcinoma | 11 Participants | 21 Participants | 10 Participants |
| Histology Subtype Clear Cell Component | 0 Participants | 0 Participants | 0 Participants |
| Histology Subtype Clear Cell (non-component) | 0 Participants | 0 Participants | 0 Participants |
| Histology Subtype Large Cell Carcinoma | 0 Participants | 0 Participants | 0 Participants |
| Histology Subtype Micropapillary Variant | 0 Participants | 0 Participants | 0 Participants |
| Histology Subtype Non-Small Cell Lung Cancer, NOS | 1 Participants | 1 Participants | 0 Participants |
| Histology Subtype Other | 0 Participants | 0 Participants | 0 Participants |
| Histology Subtype Papillary | 0 Participants | 0 Participants | 0 Participants |
| Histology Subtype Poorly Differentiated Carcinoma | 3 Participants | 3 Participants | 0 Participants |
| Histology Subtype Sarcomatoid | 0 Participants | 0 Participants | 0 Participants |
| Histology Subtype Small Cell Carcinoma | 0 Participants | 0 Participants | 0 Participants |
| Histology Subtype Squamous Cell Carcinoma | 17 Participants | 21 Participants | 4 Participants |
| Histology Subtype Transitional Cell Carcinoma | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Non-Hispanic | 31 Participants | 42 Participants | 11 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 5 Participants | 6 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Unknown | 0 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Race White | 26 Participants | 35 Participants | 9 Participants |
| Sex: Female, Male Female | 13 Participants | 22 Participants | 9 Participants |
| Sex: Female, Male Male | 19 Participants | 24 Participants | 5 Participants |
| Substance use : Number of Cigarettes 1 | 1 Participants | 3 Participants | 2 Participants |
| Substance use : Number of Cigarettes 2 | 6 Participants | 8 Participants | 2 Participants |
| Substance use : Number of Cigarettes 3 | 25 Participants | 35 Participants | 10 Participants |
| Substance use : Number of Cigarettes 9 | 0 Participants | 0 Participants | 0 Participants |
| Substance use : Number of Cigars 1 | 25 Participants | 32 Participants | 7 Participants |
| Substance use : Number of Cigars 9 | 7 Participants | 14 Participants | 7 Participants |
| Substance use : Number of pipefuls 1 | 26 Participants | 33 Participants | 7 Participants |
| Substance use : Number of pipefuls 9 | 6 Participants | 13 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 11 / 14 | 0 / 0 | 19 / 32 |
| other Total, other adverse events | 14 / 14 | 0 / 0 | 32 / 32 |
| serious Total, serious adverse events | 8 / 14 | 0 / 0 | 11 / 32 |
Outcome results
Primary
Phase II: Disease Assessment for Progression-Free Survival (PFS)
To evaluate progression-free survival (PFS) for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria. PFS is defined as the duration of time from date of registration to time of progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: From date of registration to time of first documented progression or death, whichever occurs first (estimate 9 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I, Cohort 1 | Phase II: Disease Assessment for Progression-Free Survival (PFS) | 6.2 months |
Primary
Phase II: Objective Response Rate
To evaluate objective response rate for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: From the start of treatment until progression or death up to 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I, Cohort 1 | Phase II: Objective Response Rate | 16 Participants |
Primary
Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose
To determine the recommended Phase II dose (RP2D) of MK-3475 and evaluate the safety and tolerability of the combination of MK-3475 with carboplatin/nab-paclitaxel for the first line treatment of phase I participants with advanced NSCLC per CTCAE v4.0 criteria by summarizing the number of adverse events experienced by subjects.
Time frame: Begin C1D1 and every 2 chemotherapy cycles (6 weeks) thereafter, for up to 2 years or until unacceptable toxicity.
Population: No subjects had been enrolled to Phase I, cohort 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I, Cohort 1 | Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose | Patient had at least one adverse event of any grade | 14 Participants |
| Phase I, Cohort 1 | Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose | Patient had at least one grade 3 or greater adverse event | 14 Participants |
| Phase I, Cohort 1 | Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose | Patient had at least one grade 3 or greater treatment related adverse event | 12 Participants |
| Phase I, Cohort 1 | Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose | Patient having serious adverse event | 8 Participants |
| Phase I, Cohort 2 | Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose | Patient having serious adverse event | 0 Participants |
| Phase I, Cohort 2 | Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose | Patient had at least one adverse event of any grade | 0 Participants |
| Phase I, Cohort 2 | Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose | Patient had at least one grade 3 or greater treatment related adverse event | 0 Participants |
| Phase I, Cohort 2 | Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose | Patient had at least one grade 3 or greater adverse event | 0 Participants |
Secondary
All Phases: Assessment of Association of PD-L1 Expression on PFS
To evaluate the association of PD-L1 expression on PFS for all participants receiving MK-3475. PD-L1 will be categorized as positive (≥50% expression) or negative (\<50% expression) from pre-treatment and post-treatment biopsies. PFS will be summarized by PD-L1 expression.
Time frame: From date of registration to time of first documented progression. (Measurable disease will be assessed after every 2 chemotherapy cycles [every 6 weeks thereafter for up to 2 years or until unacceptable toxicity]).
Population: 34 of the 46 subjects have staining information available
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase I, Cohort 1 | All Phases: Assessment of Association of PD-L1 Expression on PFS | 0-49% | 4.2 months |
| Phase I, Cohort 1 | All Phases: Assessment of Association of PD-L1 Expression on PFS | >=50% | 4.6 months |
| Phase I, Cohort 1 | All Phases: Assessment of Association of PD-L1 Expression on PFS | 0% | 5.6 months |
Secondary
Phase I: Disease Assessment for Anti-Tumor Activity
To evaluate anti-tumor activity for phase I participants will be reported as a percentage change in the sum of the dimensions of all measurable lesions as defined by RECIST 1.1 criteria.
Time frame: From date of registration to time of first documented progression. (Measurable disease will be assessed after every 2 chemotherapy cycles [every 6 weeks thereafter for up to 2 years or until unacceptable toxicity]).
Population: No subjects had been enrolled to Phase I, cohort 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I, Cohort 1 | Phase I: Disease Assessment for Anti-Tumor Activity | -6.9457 percent change |
Secondary
Phase I: Disease Assessment for Progression-Free Survival (PFS)
To evaluate progression-free survival (PFS) and objective response for phase I participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: From date of registration to time of first documented progression or death, whichever occurs first (estimate 9 months)
Population: No subjects had been enrolled to Phase I, Cohort 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I, Cohort 1 | Phase I: Disease Assessment for Progression-Free Survival (PFS) | 5.2 months |
Secondary
Phase II: Disease Assessment for Anti-Tumor Activity
To evaluate anti-tumor activity for phase I participants will be reported as a percentage change in the sum of the dimensions of all measurable lesions as defined by RECIST 1.1 criteria.
Time frame: From date of registration to time of first documented progression. (Measurable disease will be assessed after every 2 chemotherapy cycles [every 6 weeks thereafter for up to 2 years or until unacceptable toxicity]).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I, Cohort 1 | Phase II: Disease Assessment for Anti-Tumor Activity | -46.7731 percent change |
Secondary
Phase II: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
To evaluate the safety and tolerability of the combination of MK-3475 with carboplatin/nab-paclitaxel for the first line treatment of phase II participants with advanced NSCLC per CTCAE v4.0. Safety and tolerability is defined as rates of Grade 1-5 toxicity according to CTCAE v4.
Time frame: Begin C1D1 and every 2 cycles (6 weeks) thereafter, for up to 2 years or until unacceptable toxicity.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I, Cohort 1 | Phase II: Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Patient had at least one adverse event of any grade. | 32 Participants |
| Phase I, Cohort 1 | Phase II: Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Patient had at least one grade 3 or greater adverse event. | 31 Participants |
| Phase I, Cohort 1 | Phase II: Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Patient had at least one grade 3 or greater treatment related adverse event. | 27 Participants |
| Phase I, Cohort 1 | Phase II: Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Patient having serious adverse event. | 11 Participants |
Secondary
Phase II: Overall Survival (OS)
To evaluate overall survival rates for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC.
Time frame: From date of registration to date of death from any cause up to 42 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I, Cohort 1 | Phase II: Overall Survival (OS) | 16 months |
Secondary
Phase I : Objective Response Rate
To evaluate objective response rate for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria. Objective response rate (ORR), is defined as the proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST).
Time frame: From the start of treatment until progression or death up to 11 months.
Population: No subjects had been enrolled to Phase I, Cohort 2.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I, Cohort 1 | Phase I : Objective Response Rate | 1 Participants |
Secondary
Phase I: Overall Survival (OS)
To evaluate overall survival rates for phase I participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC.
Time frame: From date of registration to date of death from any cause up to 49 months.
Population: No subjects had been enrolled in Phase I. cohort 2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I, Cohort 1 | Phase I: Overall Survival (OS) | 13 months |