DUMAS: Neo-Adjuvant Immunotherapy for Pancoast Tumors

Inclusion Criteria:

1. Previously untreated patients with histologically- or cytologically- documentedNSCLC diagnosed with Pancoast tumor according to 8th edition of the TNM (stagesIIB, IIIA and T3N2 (IIIB) patients)

2. PET/CT including IV contrast (CT of diagnostic quality) will be performed atbaseline (28 days +10 before enrollment) to rule out the presence of distantdisease. Also, a brain CT-SCAN or brain MRI will be done at baseline

3. Positive mediastinal lymph nodes by PET-CT must be confirmed histologically.Mediastinal involvement may be considered without the need for histologicalconfirmation when there is a mass of lymph nodes in which the margins cannot bedistinguished

4. Measurable or evaluable disease (according to RECIST 1.1 criteria)

5. ECOG (Performance status) 0-2

6. Patients with a life expectancy of at least more than 12 weeks

7. Patients aged > 18 years and ≤ 75 years

• 8 Screening laboratory values must meet the study criteria and should be obtainedwithin 14 days prior to enrollment

9. Correct lung function without bronchodilators, defined by forced expiratoryvolume in 1 second (FEV1) >40% of the predicted normal volume, and a pulmonarydiffusing capacity for carbon monoxide (DLCO) >40% of the predicted normalvalue

10. All patients are notified of the investigational nature of this study andsigned a written informed consent in accordance with institutional and nationalguidelines, including the Declaration of Helsinki prior to any trial-relatedintervention

11. Women of childbearing potential, including women who had their last menstrualperiod in the last 2 years, must have a negative serum or urine pregnancy testwithin 7 days before enrollment.

12. All sexually active men and women of childbearing potential must use aneffective contraceptive method during the study treatment and for a period ofat least 12 months following the last administration of trial drugs

13. Patient capable of proper therapeutic compliance and accessible for correctfollow-up.

Exclusion Criteria:

1. Patients that receive previous treatment with antineoplastic drugs, chestradiotherapy, or previous surgery for lung cancer or for another reason

2. Pleural or pericardial effusion: Both will be considered indicative ofmetastatic disease unless proven otherwise. Those that, even beingcytologically negative for malignancy, are exudates, will also be excluded.Patients with pleural effusion not visible on chest X-ray or too small toperform diagnostic puncture safely may be included.

3. Patients with a weight loss >10% in the 3 months prior to the study entry

4. All patients carrying activating mutations in the TK domain of EGFR or anyvariety of alterations in the ALK gene or ROS1 mutations.

5. Patients with active, known or suspected autoimmune disease. Subjects withvitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmunethyroiditis only requiring hormone replacement or unexpected conditions ofrecurrence in the absence of an external trigger are allowed to be included.

6. Patients with symptomatic neuropathy > grade 1 according to the CTCAE v5.0 andthat were not related to the tumor

7. Patients with a condition requiring systemic treatment with eithercorticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressivemedications within 14 days of enrollment. Inhaled or topical steroids, andadrenal replacement steroid doses > 10 mg daily prednisone equivalent, arepermitted in the absence of active autoimmune disease.

8. Patients with a history of interstitial lung disease cannot be included if theyhave symptomatic ILD (Grade 3-4) and/or poor lung function. In case of doubtplease contact trial team.

9. Patients with other active malignancy requiring concurrent intervention and/orconcurrent treatment with other investigational drugs or anticancer therapy

10. Patients with uncontrolled comorbidities that may affect the clinical trialcompliance

11. Patients with previous malignancies (except non-melanoma skin cancers, and thefollowing in situ cancers: bladder, gastric, colon, endometrial,cervical/dysplasia, melanoma, or breast) are excluded unless a completeremission was achieved at least 5 years prior to study entry and no additionaltherapy is required during the study period.

12. Any medical, mental, neurological or psychological condition which in theopinion of the investigator would not permit the patient to complete the studyor understand the patient information sheet.

13. Patients in any psychological, familiar, sociological or geographical situationthat may hinder compliance with the study protocol and/or the follow up

14. Patients who have had prior treatment with an anti-PD-1, anti-PD-L1,anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specificallytargeting T-cell co-stimulation or immune checkpoint pathways

15. Patients with positive test for hepatitis B virus surface antigen (HBV sAg) orhepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronicinfection

16. Patients with known history of testing positive for human immunodeficiencyvirus (HIV) or known acquired immunodeficiency syndrome (AIDS).

17. Patients with know hypersensitivity to drugs with a structure similar to thestudy drug and/or history of allergy to study drug components excipients

18. Women who are pregnant or in the period of breastfeeding

19. Sexually active men and women of childbearing potential who are not willing touse an effective contraceptive method during the study