Stage IA Lung Non-Small Cell Carcinoma AJCC v7, Stage IB Lung Non-Small Cell Carcinoma AJCC v7, Stage IIA Lung Non-Small Cell Carcinoma AJCC v7, Stage IIB Lung Non-Small Cell Carcinoma AJCC v7, Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage II Lung Non-Small Cell Cancer AJCC v7, Stage I Lung Non-Small Cell Cancer AJCC v7
Conditions
Brief summary
This phase II trial studies how well nivolumab works when given alone and in combination with ipilimumab or chemotherapy in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cisplatin, docetaxel, and pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab with ipilimumab or chemotherapy may work better in treating patients with non-small cell lung cancer compared to chemotherapy alone.
Detailed description
PRIMARY OBJECTIVE: I. To determine the major pathologic response rate (MPRR) in patients treated with induction nivolumab, nivolumab plus ipilimumab, and nivolumab plus platinum-based chemotherapy. SECONDARY OBJECTIVES: I. Toxicity (assessed by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 4). II. Peri-operative morbidity and mortality. III. CD8 positive (+) tumor infiltrating lymphocytes (TILs) in resected tumor tissues of patients treated with nivolumab alone and nivolumab plus ipilimumab and nivolumab plus platinum-based chemotherapy. IV. Quantification of CD8+ TILs will be assessed by counting the cells positive for staining with an anti-CD8 antibody by immunohistochemistry in five random square areas (1 mm\^2 each) in both intratumoral and peritumoral compartments using the automated Aperio system. V. Response rates to induction treatment (by Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1). VI. Recurrence-free survival. VII. Overall survival. VIII. To correlate major pathologic response with recurrence-free and overall survival. IX. Complete resection (R0) rate. X. Pathologic complete response (pCR) in resected tumor specimens. XI. To correlate response assessed by imaging studies with outcomes (both major pathologic response to treatment and long-term recurrence-free survival). XII. To correlate blood, tissue, and stool-based biomarkers with efficacy and toxicity. EXPLORATORY OBJECTIVES: I. To identify novel prognostic and predictive markers present at diagnosis. II. To determine modulation of markers by induction immunotherapy and/or immunotherapy plus platinum-based chemotherapy in order to inform future translational studies. OUTLINE: Patients are randomized to Arms A and B and enrolled in Arm C or D after completion of enrollment to Arms A and B. ARM A: Patients receive nivolumab intravenously (IV) over 60 minutes on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive nivolumab as in Arm A and receive ipilimumab IV over 90 minutes on day 1 in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive nivolumab IV over 30 minutes and cisplatin IV over 2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour or pemetrexed IV over 10 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. ARM D: Patients receive ipilimumab IV over 90 minutes on day 1, nivolumab IV over 30 minutes on days 1, 22, and 43, and cisplatin (or carboplatin) IV over 2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour or pemetrexed IV over 10 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. After completion of study treatment and surgery, patients are followed up at 8 weeks.
Interventions
DRUGCarboplatin
Given IV
DRUGCisplatin
Given IV
DRUGDocetaxel
Given IV
BIOLOGICALIpilimumab
Given IV
BIOLOGICALNivolumab
Given IV
DRUGPemetrexed
Given IV
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
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 previously untreated non-small cell lung cancer. If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study. Neuroendocrine carcinomas are not eligible. Carcinomas with neuroendocrine differentiation are eligible * Patients with stage IA or stage IB \< 4 cm (according to American Joint Committee on Cancer \[AJCC\] 7th edition) are eligible for randomization into arms A and B only. Patients with stage IB \>= 4 cm, IIA, IIB, or IIIA disease (according to AJCC 7th edition) are eligible for randomization into arms A, and B, and for enrollment into arms C and D * Patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor * All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease * The patient must be a suitable candidate for surgery, in the opinion of the treating physician * Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation * Eastern Cooperative Oncology Group (ECOG) performance status score 0-1 * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L * Hemoglobin \>= 8.0 g/dL * Platelets \>= 100 x 10\^9/L * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin \< 3.0 mg/dL) * Creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance \>= 50 mL/min
Exclusion criteria
* Prior systemic therapy or radiation therapy for treatment of the current lung cancer * Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug * Pregnant or lactating female: Women of childbearing potential (WOCB) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 72 hours prior to the start of nivolumab; Women of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes * Unwillingness or inability to follow the procedures required in the protocol * Patients with pre-existing sensorineural hearing impairment/loss or newly diagnosed as documented by an audiology assessment performed prior to study enrollment may not be eligible for cisplatin and may be dispositioned to carboplatin, as determined by the treating physician. * Patients with a history of severe hypersensitivity reaction to taxotere and or polysorbate 80 must be excluded * Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results * Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll * Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted * Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody * Known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid indicating acute or chronic infection * Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome * History of severe hypersensitivity reaction to any monoclonal antibody and/or to study drug components * Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study * Patients who are sexually active, with preserved reproductive capacity, and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during and after the trial * Women of child bearing potential (WOCBP) should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug(s); Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year; Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; Women who are not of childbearing potential as well as azoospermic men do not require contraception * Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathologic Response (mPR) | The lung resection specimen was collected at surgery. | The percentage of viable tumor cells was averaged across all reviewed tumor slides from the lung resection specimen. The specimen was reviewed by two pathologists and average score was used. Tumors with ≤ 10% of viable tumor cells were considered to have undergone MPR. Patients who did not have surgery was considered to be no MPR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) | The lung resection specimen was collected at surgery. | The percentage of viable tumor cells was averaged across all reviewed tumor slides from the lung resection specimen. The specimen was reviewed by two pathologists and average score was used. Tumors with 0% of viable tumor cells were considered to have undergone pCR. Patients who did not have surgery was considered to be no pCR. |
| Radiographic Response | Reassessment after induction therapy | Radiographic response to induction treatment was assessed by RECIST version 1.1 |
| Overall Survival (OS) | In Arms A and B, the cutoff date was 2020-2-25. The median follow-up time frame was 22.2 months. In Arms C and D, the cutoff date was 2022-7-18. The median follow-up time frames were 39.2 and 24.0 months respectively | Overall survival was defined as the time from randomization (in Arm A and Arm B) or treatment initiation (in Arm C and Arm D) to the time of death from all causes or to the time of last follow-up. |
| Event-free Survival (EFS) | In Arms A and B, the cutoff date was 2020-2-25. The median follow-up time frame was 22.2 months. In Arms C and D, the cutoff date was 2022-7-18. The median follow-up time frames were 39.2 and 24.0 months respectively. | EFS was defined as the time from randomization (in Arm A and Arm B) or treatment initiation (in Arm C and Arm D) to any progression of primary lung cancer precluding planned surgery, any progression or recurrence (as assessed by imaging and/or histopathologically) of primary lung cancer after surgery, any progression of primary lung cancer in patients without surgery or death from all causes or to the time of last imaging. |
| Residual Tumor Classification | At surgery | The residual tumor (R) classification measures how well the lung tumor was removed by surgery in the anatomic extent. R0 means a complete resection. R1 means a macroscopically complete resection but with microscopic tumor at the surgical margin. R2 means a resection that leaves gross tumor behind. R0 resection is a better surgical outcome than R1, R2 resections and R2 is the worst surgical outcome. The number of R0, R1 and R2 resections were reported among the patients who underwent surgery. |
| 30-day Postoperative Complication | Within 30 days after surgery | The number of patients who had complications including pulmonary, cardiac, gastrointestinal, genitourinary, neurological, and wound within 30 days after surgery |
| 90-day Mortality | Within 90 days after surgery | The number of patients who died within 90 days after surgery |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTina Cascone
M.D. Anderson Cancer Center
Participant flow
Recruitment details
Phase 2, multi-arm study at the University of Texas MD Anderson Cancer Center recruited patients with resectable stage I-IIIA non-small cell lung cancer. It started on 2017-6-9. The first patient gave consent on 2017-6-16. Patients were randomized to either Arm A - Nivolumab or Arm B - Nivolumab + Ipilimumab. After completion, patients were enrolled in Arm C - Nivolumab + Chemotherapy from 2018-12-14 to 2019-7-22 and Arm D - Nivolumab + Ipilimumab + Chemotherapy from 2019-12-30 to 2020-12-1.
Pre-assignment details
Fifty-three patients were enrolled in Arm A and Arm B, 9 of them were screen failures. Twenty-three patients were enrolled in Arm C, 1 of them was screen failure. Twenty-five patients were enrolled in Arm D, 3 of them were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Arm A - Nivolumab Induction nivolumab 3 mg/kg intravenous on days 1, 15, and 29 followed by surgery within 3 to 6 weeks. | 23 |
| Arm B - Nivolumab + Ipilimumab Induction nivolumab 3 mg/kg intravenous (IV) on days 1, 15, and 29 plus ipilimumab 1 mg/kg IV on day 1 followed by surgery within 3 to 6 weeks. | 21 |
| Arm C - Nivolumab + Chemotherapy Induction nivolumab 3 mg/kg intravenous (IV) plus cisplatin and docetaxel (or pemetrexed) IV on days 1, 22, and 43 followed by surgery within 3 to 6 weeks. | 22 |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy Induction nivolumab 3 mg/kg intravenous (IV) plus cisplatin (or carboplatin) and docetaxel (or pemetrexed) IV on days 1, 22, and 43 plus ipilimumab 1 mg/kg IV on day 1 followed by surgery within 3 to 6 weeks. | 22 |
| Total | 88 |
Baseline characteristics
| Characteristic | Arm A - Nivolumab | Arm B - Nivolumab + Ipilimumab | Arm C - Nivolumab + Chemotherapy | Arm D - Nivolumab + Ipilimumab + Chemotherapy | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 13 Participants | 12 Participants | 9 Participants | 46 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 8 Participants | 10 Participants | 13 Participants | 42 Participants |
| Age, Continuous | 65.9 YEARS | 66.2 YEARS | 69.5 YEARS | 63.1 YEARS | 65.9 YEARS |
| Histology Adenocarcinoma | 13 Participants | 13 Participants | 16 Participants | 13 Participants | 55 Participants |
| Histology Adenosquamous carcinoma | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Histology Carcinoma with neuroendocrine features | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Histology Large cell carcinoma | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Histology Not otherwise specified NSCLC | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Histology Sarcomatoid carcinoma | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Histology Squamous cell carcinoma | 10 Participants | 7 Participants | 5 Participants | 5 Participants | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 0 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 21 Participants | 16 Participants | 19 Participants | 18 Participants | 74 Participants |
| Region of Enrollment United States | 23 participants | 21 participants | 22 participants | 22 participants | 88 participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 12 Participants | 7 Participants | 35 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 10 Participants | 15 Participants | 53 Participants |
| Smoking status Current smoker | 4 Participants | 6 Participants | 0 Participants | 4 Participants | 14 Participants |
| Smoking status Former smoker | 14 Participants | 12 Participants | 17 Participants | 13 Participants | 56 Participants |
| Smoking status Never smoker | 5 Participants | 3 Participants | 5 Participants | 5 Participants | 18 Participants |
| Stage Stage IA | 4 Participants | 4 Participants | 0 Participants | 0 Participants | 8 Participants |
| Stage Stage IB | 7 Participants | 8 Participants | 1 Participants | 0 Participants | 16 Participants |
| Stage Stage IIA | 2 Participants | 5 Participants | 6 Participants | 2 Participants | 15 Participants |
| Stage Stage IIB | 5 Participants | 0 Participants | 4 Participants | 7 Participants | 16 Participants |
| Stage Stage IIIA | 5 Participants | 4 Participants | 11 Participants | 13 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 23 | 1 / 21 | 3 / 22 | 3 / 22 |
| other Total, other adverse events | 22 / 23 | 21 / 21 | 22 / 22 | 22 / 22 |
| serious Total, serious adverse events | 4 / 23 | 3 / 21 | 7 / 22 | 3 / 22 |
Outcome results
Primary
Major Pathologic Response (mPR)
The percentage of viable tumor cells was averaged across all reviewed tumor slides from the lung resection specimen. The specimen was reviewed by two pathologists and average score was used. Tumors with ≤ 10% of viable tumor cells were considered to have undergone MPR. Patients who did not have surgery was considered to be no MPR.
Time frame: The lung resection specimen was collected at surgery.
Population: Intention-to-treat popluation
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A - Nivolumab | Major Pathologic Response (mPR) | MPR | 5 Participants |
| Arm A - Nivolumab | Major Pathologic Response (mPR) | No MPR | 18 Participants |
| Arm B - Nivolumab + Ipilimumab | Major Pathologic Response (mPR) | No MPR | 13 Participants |
| Arm B - Nivolumab + Ipilimumab | Major Pathologic Response (mPR) | MPR | 8 Participants |
| Arm C - Nivolumab + Chemotherapy | Major Pathologic Response (mPR) | MPR | 7 Participants |
| Arm C - Nivolumab + Chemotherapy | Major Pathologic Response (mPR) | No MPR | 15 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Major Pathologic Response (mPR) | MPR | 11 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Major Pathologic Response (mPR) | No MPR | 11 Participants |
Secondary
30-day Postoperative Complication
The number of patients who had complications including pulmonary, cardiac, gastrointestinal, genitourinary, neurological, and wound within 30 days after surgery
Time frame: Within 30 days after surgery
Population: Intention-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A - Nivolumab | 30-day Postoperative Complication | Complication | 8 Participants |
| Arm A - Nivolumab | 30-day Postoperative Complication | No surgery | 2 Participants |
| Arm A - Nivolumab | 30-day Postoperative Complication | No complication | 13 Participants |
| Arm B - Nivolumab + Ipilimumab | 30-day Postoperative Complication | Complication | 5 Participants |
| Arm B - Nivolumab + Ipilimumab | 30-day Postoperative Complication | No surgery | 5 Participants |
| Arm B - Nivolumab + Ipilimumab | 30-day Postoperative Complication | No complication | 11 Participants |
| Arm C - Nivolumab + Chemotherapy | 30-day Postoperative Complication | No complication | 15 Participants |
| Arm C - Nivolumab + Chemotherapy | 30-day Postoperative Complication | Complication | 7 Participants |
| Arm C - Nivolumab + Chemotherapy | 30-day Postoperative Complication | No surgery | 0 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | 30-day Postoperative Complication | Complication | 13 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | 30-day Postoperative Complication | No surgery | 2 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | 30-day Postoperative Complication | No complication | 7 Participants |
Secondary
90-day Mortality
The number of patients who died within 90 days after surgery
Time frame: Within 90 days after surgery
Population: Intention-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A - Nivolumab | 90-day Mortality | Dead | 1 Participants |
| Arm A - Nivolumab | 90-day Mortality | No surgery | 2 Participants |
| Arm A - Nivolumab | 90-day Mortality | Alive | 20 Participants |
| Arm B - Nivolumab + Ipilimumab | 90-day Mortality | Dead | 0 Participants |
| Arm B - Nivolumab + Ipilimumab | 90-day Mortality | No surgery | 5 Participants |
| Arm B - Nivolumab + Ipilimumab | 90-day Mortality | Alive | 16 Participants |
| Arm C - Nivolumab + Chemotherapy | 90-day Mortality | Alive | 22 Participants |
| Arm C - Nivolumab + Chemotherapy | 90-day Mortality | Dead | 0 Participants |
| Arm C - Nivolumab + Chemotherapy | 90-day Mortality | No surgery | 0 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | 90-day Mortality | Dead | 0 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | 90-day Mortality | No surgery | 2 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | 90-day Mortality | Alive | 20 Participants |
Secondary
Event-free Survival (EFS)
EFS was defined as the time from randomization (in Arm A and Arm B) or treatment initiation (in Arm C and Arm D) to any progression of primary lung cancer precluding planned surgery, any progression or recurrence (as assessed by imaging and/or histopathologically) of primary lung cancer after surgery, any progression of primary lung cancer in patients without surgery or death from all causes or to the time of last imaging.
Time frame: In Arms A and B, the cutoff date was 2020-2-25. The median follow-up time frame was 22.2 months. In Arms C and D, the cutoff date was 2022-7-18. The median follow-up time frames were 39.2 and 24.0 months respectively.
Population: Intention-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab | Event-free Survival (EFS) | NA Months |
| Arm B - Nivolumab + Ipilimumab | Event-free Survival (EFS) | NA Months |
| Arm C - Nivolumab + Chemotherapy | Event-free Survival (EFS) | NA Months |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Event-free Survival (EFS) | NA Months |
Secondary
Overall Survival (OS)
Overall survival was defined as the time from randomization (in Arm A and Arm B) or treatment initiation (in Arm C and Arm D) to the time of death from all causes or to the time of last follow-up.
Time frame: In Arms A and B, the cutoff date was 2020-2-25. The median follow-up time frame was 22.2 months. In Arms C and D, the cutoff date was 2022-7-18. The median follow-up time frames were 39.2 and 24.0 months respectively
Population: Intention-to-treat population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A - Nivolumab | Overall Survival (OS) | NA Months |
| Arm B - Nivolumab + Ipilimumab | Overall Survival (OS) | NA Months |
| Arm C - Nivolumab + Chemotherapy | Overall Survival (OS) | NA Months |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Overall Survival (OS) | NA Months |
Secondary
Pathologic Complete Response (pCR)
The percentage of viable tumor cells was averaged across all reviewed tumor slides from the lung resection specimen. The specimen was reviewed by two pathologists and average score was used. Tumors with 0% of viable tumor cells were considered to have undergone pCR. Patients who did not have surgery was considered to be no pCR.
Time frame: The lung resection specimen was collected at surgery.
Population: Intention-to-treat popluation
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A - Nivolumab | Pathologic Complete Response (pCR) | pCR | 2 Participants |
| Arm A - Nivolumab | Pathologic Complete Response (pCR) | No pCR | 21 Participants |
| Arm B - Nivolumab + Ipilimumab | Pathologic Complete Response (pCR) | No pCR | 15 Participants |
| Arm B - Nivolumab + Ipilimumab | Pathologic Complete Response (pCR) | pCR | 6 Participants |
| Arm C - Nivolumab + Chemotherapy | Pathologic Complete Response (pCR) | No pCR | 18 Participants |
| Arm C - Nivolumab + Chemotherapy | Pathologic Complete Response (pCR) | pCR | 4 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Pathologic Complete Response (pCR) | pCR | 4 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Pathologic Complete Response (pCR) | No pCR | 18 Participants |
Secondary
Radiographic Response
Radiographic response to induction treatment was assessed by RECIST version 1.1
Time frame: Reassessment after induction therapy
Population: Intention-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A - Nivolumab | Radiographic Response | PD | 3 Participants |
| Arm A - Nivolumab | Radiographic Response | PR | 5 Participants |
| Arm A - Nivolumab | Radiographic Response | Not evaluable | 0 Participants |
| Arm A - Nivolumab | Radiographic Response | SD | 15 Participants |
| Arm A - Nivolumab | Radiographic Response | CR | 0 Participants |
| Arm B - Nivolumab + Ipilimumab | Radiographic Response | SD | 13 Participants |
| Arm B - Nivolumab + Ipilimumab | Radiographic Response | PD | 3 Participants |
| Arm B - Nivolumab + Ipilimumab | Radiographic Response | Not evaluable | 1 Participants |
| Arm B - Nivolumab + Ipilimumab | Radiographic Response | PR | 3 Participants |
| Arm B - Nivolumab + Ipilimumab | Radiographic Response | CR | 1 Participants |
| Arm C - Nivolumab + Chemotherapy | Radiographic Response | SD | 13 Participants |
| Arm C - Nivolumab + Chemotherapy | Radiographic Response | CR | 0 Participants |
| Arm C - Nivolumab + Chemotherapy | Radiographic Response | PR | 9 Participants |
| Arm C - Nivolumab + Chemotherapy | Radiographic Response | PD | 0 Participants |
| Arm C - Nivolumab + Chemotherapy | Radiographic Response | Not evaluable | 0 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Radiographic Response | PD | 1 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Radiographic Response | PR | 6 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Radiographic Response | CR | 0 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Radiographic Response | SD | 14 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Radiographic Response | Not evaluable | 1 Participants |
Secondary
Residual Tumor Classification
The residual tumor (R) classification measures how well the lung tumor was removed by surgery in the anatomic extent. R0 means a complete resection. R1 means a macroscopically complete resection but with microscopic tumor at the surgical margin. R2 means a resection that leaves gross tumor behind. R0 resection is a better surgical outcome than R1, R2 resections and R2 is the worst surgical outcome. The number of R0, R1 and R2 resections were reported among the patients who underwent surgery.
Time frame: At surgery
Population: Intention-to-treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A - Nivolumab | Residual Tumor Classification | R0 | 21 Participants |
| Arm A - Nivolumab | Residual Tumor Classification | R1 | 0 Participants |
| Arm A - Nivolumab | Residual Tumor Classification | R2 | 0 Participants |
| Arm A - Nivolumab | Residual Tumor Classification | No surgery | 2 Participants |
| Arm B - Nivolumab + Ipilimumab | Residual Tumor Classification | R1 | 0 Participants |
| Arm B - Nivolumab + Ipilimumab | Residual Tumor Classification | R2 | 0 Participants |
| Arm B - Nivolumab + Ipilimumab | Residual Tumor Classification | No surgery | 5 Participants |
| Arm B - Nivolumab + Ipilimumab | Residual Tumor Classification | R0 | 16 Participants |
| Arm C - Nivolumab + Chemotherapy | Residual Tumor Classification | R2 | 1 Participants |
| Arm C - Nivolumab + Chemotherapy | Residual Tumor Classification | R1 | 1 Participants |
| Arm C - Nivolumab + Chemotherapy | Residual Tumor Classification | No surgery | 0 Participants |
| Arm C - Nivolumab + Chemotherapy | Residual Tumor Classification | R0 | 20 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Residual Tumor Classification | No surgery | 2 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Residual Tumor Classification | R1 | 1 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Residual Tumor Classification | R0 | 19 Participants |
| Arm D - Nivolumab + Ipilimumab + Chemotherapy | Residual Tumor Classification | R2 | 0 Participants |