Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
NSCLC, lung cancer, Gemzar, Pembrolizumab, Anti-PD-1, Immunotherapy
Brief summary
This is a study for patients with previously-treated advanced non-small cell lung cancer (NSCLC). The study will evaluate the safety of adding an investigational drug, MK-3475 to standard treatment with gemcitabine. The study will also try to identify the best dose of MK-3475 to give in combination with gemcitabine.
Detailed description
This study is an open-label, non-randomized phase I study, followed by open-label non-randomized phase II study. The first cohort of patients will receive 200 milligrams (mg) of MK-3475 by intravenous infusion over a 21-day period called a cycle along with Gemcitabine 1250 mg/m2 given on Days 1 and 8 of each 21-day cycle for up to 6 cycles. Patients will be seen in the study clinic 12 times over 126 days for an evaluation of signs and symptoms that may represent drug toxicity. Patients may continue to receive MK-3475 (without gemcitabine) for up to 2 years.
Interventions
DRUGMK-3475
Investigational drug.
DRUGGemcitabine
Standard care drug.
Sponsors
Providence Health & Services
Merck Sharp & Dohme LLC
Providence Cancer Center, Earle A. Chiles Research Institute
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
* Women or men with advanced, histologically proven NSCLC. * Patients must have received at least one but no more than three prior systemic therapies for advanced disease. * Any toxicity related to prior therapies that, in the opinion of the investigator, would potentially be worsened with anti-PD1 therapy or gemcitabine should be resolved to less than Grade 1. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * Women of childbearing potential must have a negative pregnancy test * Ability to give informed consent and comply with the protocol. * Anticipated survival minimum 3 months. * Prior therapy with investigational agents must have been completed at least 3 weeks prior to study enrollment. * Patients must have normal organ and marrow function as seen on protocol-defined blood test results * Archived tumor tissue (minimum of 8 slides for paraffin-embedded tumor tissue) available * Measurable disease by RECIST 1.1 criteria. * Treated brain metastases will be allowed, provided they are asymptomatic. * Radiation for symptomatic lesions outside the Central nervous system (CNS) must have been completed at least 2 weeks prior to study enrollment.
Exclusion criteria
* Prior therapy with any anti-PD-1, anti-PD-L1, or anti-CTLA4 antibody. * Prior therapy with gemcitabine. * Prior complications from radiation, such as history of radiation pneumonitis or pulmonary edema that, in the opinion of the investigator, may have risk of increasing toxicity with anti-PD1 therapy. * Active autoimmune disease except vitiligo or stable hypothyroidism. * Active and ongoing steroid use, except for non-systemically absorbed treatments (such as inhaled or topical steroid therapy for asthma, cardiopulmonary disease (COPD), allergic rhinitis). * Active other malignancy, except for controlled basal cell skin carcinoma. * HIV positive and/or Hepatitis B or C positive. * Other medical or psychiatric conditions that in the opinion of the Principal Investigator would preclude safe participation in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities | 126 Days (six 21-day cycles) | Patients are seen in clinic 12 times over 126 days to determine any changes in signs or symptoms that may represent drug toxicity. Drug toxicity is defined as events that required holding or delaying treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 2 years | Patients will have CT scans after every two cycles for up to 2 years to assess changes in tumor sizes. |
| Overall Survival | Every 12 weeks (up to 2 years) | Patients will be contacted every 12 weeks following end of treatment to determine survival status until death, withdrawal of consent, or the end of the study, whichever occurs first. |
| Disease Response | up to 2 years | Patients will have CT scans to assess changes in tumor sizes. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRachel Sanborn, MD
Providence Health & Services
Participant flow
Pre-assignment details
Patients enrolled in the Phase I and II portions were evaluated together for outcomes. There were no DLTs, so no dose de-escalation was triggered and all 16 patients then received the same therapy. As such, outcomes were analyzed together.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 76 years |
| Baseline ECOG Performance Status ECOG PS 0 (Asymptomatic) | 2 Participants |
| Baseline ECOG Performance Status ECOG PS 1 (Symptomatic but completely ambulatory) | 14 Participants |
| Baseline ECOG Performance Status ECOG PS 2 (Symptomatic, <50% in bed during the day) | 0 Participants |
| Baseline ECOG Performance Status ECOG PS 3 (Symptomatic, >50% in bed, but not bedbound) | 0 Participants |
| Baseline ECOG Performance Status ECOG PS 4 (Bedbound) | 0 Participants |
| Baseline ECOG Performance Status ECOG PS 5 (Death) | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 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 | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
| Tumor Histology Adenocarcinoma | 12 Participants |
| Tumor Histology Non-Small Cell Lung Cancer (not otherwise specified) | 3 Participants |
| Tumor Histology Squamous Cell Carcinoma | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 14 / 16 |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 9 / 16 |
Outcome results
None listed