Ipilimumab plus Nivolumab and ChemoRadiotherapy followed by Surgery in patients with resectable and borderline resectable T3-4N0-1 NSCLC

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 29

Inclusion Criteria

1. Histologically confirmed NSCLC, a histological biopsy is mandatory
2. T3-4, N0-1 tumors based on size or upon ingrowth into the thoracic wall,
mediastinum, vertebra or diaphragm
3. Patients that are irresectable upfront, but expected to be resectable after
chemoradiotherapy induction, as per multidisciplinary tumor board evaluation
4. Be willing and able to provide written informed consent for the trial.
5. Be above 18 years of age on day of signing informed consent.
6. Have measurable disease based on RECIST 1.1. 9.
7. Have a performance status of 0-1 on the ECOG Performance Scale.
8. Demonstrate adequate organ function.

Exclusion Criteria

1. Known oncogenic drivers such as activating EGFR or BRAF mutations or ALK or
ROS1 gene rearrangements
2. Prior surgery and/or radiotherapy on the ipsilateral thorax
3. Patients deemed inoperable
4. Subjects with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) or other
immunosuppressive medications within 14 days of day 0. Inhaled or topical
steroids, and adrenal replacement steroid >10 mg daily prednisone
equivalent, are permitted in the absence of active autoimmune disease.
5. Additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, or in situ cervical cancer that has undergone potentially curative
therapy.
6. Active autoimmune disease requiring systemic steroid treatment within the
past 3 months or a documented history of clinically severe autoimmune disease,
or a syndrome that requires systemic steroids.
7. Evidence of interstitial lung disease or active, non-infectious pneumonitis.
8. Active infection requiring systemic therapy.
9. Ahistory of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
10. Active Hepatitis B or C.
11. Psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
12. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2,
anti-CTLA-4 antibody, or any other antibody or drug specifically targeting
T-cell co-stimulation or immune checkpoint pathways.
13. Patient is pregnant or breastfeeding, or expecting to conceive within the
projected duration of the trial, starting with the pre-screening or screening
visit through 23 weeks after the last dose of trial treatment.
A Woman of Childbearing Potential (WOCBP) is defined as any female who has
experienced menarche and who has not undergone surgical sterilization
(hysterectomy or bilateral oophorectomy) and is not postmenopausal. Menopause
is defined as 12 months of amenorrhea in a woman over age 45 years in the
absence of other biological or physiological causes.
WOCBP receiving nivolumab will be instructed to adhere to contraception for a
period of 5 months after the last dose of nivolumab. Men receiving nivolumab
and who are sexually active with WOCBP will be instructed to adhere to
contraception for a period of 7 months after the last dose of nivolumab.
These durations have been calculated using the upper limit of the half-life for
nivolumab (~25 days) and are based on the recommendation that WOCBP use
contraception for 5 half-lives plus 30 days, and men who are sexually active
with WOCBP use contraception for 5 half-lives plus 90 days after the last dose
of nivolumab. Females should not breastfeed while receiving nivolumab and for
any subsequent protocol-specified period. Investigators shall counsel WOCBP and
male subjects who are sexually active with WOCBP on the importance of pregnancy
prevention and the implications of an unexpected pregnancy. Investigators shall
advise WOCBP and male subjects who are sexually active with WOCBP on the use of
highly effective methods of contraception. Highly effective methods of
contraception have a failure rate of < 1% when used consistently and
correctly. Local laws and regulations may require use of a

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Safety defined as (i) the percentage of patients with adverse events (NCI<br /><br>CTCAE), and with each adverse event, the grade and the relationship to ipi/nivo<br /><br>will be assessed, and (ii) complications that lead to delays in administering<br /><br>CRT, or to cancellation of surgery, as well as the rates of post-surgical<br /><br>morbidity. Pathologic complete responses, as well as the percentage of viable<br /><br>tumor in other cases, will be assessed on all the resection specimens. </p><br>

Secondary Outcome Measures