Anti-PD-1 Re-challenge After Immune Priming by Ipilimumab and Immune Boosting by Radiotherapy in Advanced NSCLC
Still many advanced non-small cell lung cancer (NSCLC) patients do not benefit from PD-(L)1 inhibition or will eventually develop progression through secondary resistance. Inhibition of CTLA-4, application of radiotherapy together with PD-1 inhibition showed synergistic effects and is deemed safe.
• Have proven diagnosis of recurrent advanced NSCLC, irrespective of histological subtype.
• Be willing and able to provide written informed consent/assent for the trial.
• Must still have measurable disease based on RECIST 1.1 after application of study SBRT. Lesions that were irradiated prior to the study, but have progressed since irradiation but prior to study inclusion will be allowed as measurable disease.
• Must provide newly obtained tissue from a core or excisional biopsy of a tumor lesion and are willing to have a second biopsy performed from any non-irradiated lesion after the radiation and immune-modulating treatment. This lesion may be used for RECIST measurements.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Stage IV NSCLC treated with at least PD-(L)1 blockade. There is no maximum number of previous lines of systemic treatment. Patients with both primary or acquired resistance to PD-(L)1 inhibition may be considered eligible. However, in the 1st stage ≥4 of 12 patients, in the 2nd stage a total of ≥8 of 25 patients and in the 3rd stage a total of ≥27 of 54 patients need to fulfill the definition of acquired resistance. Also, a maximum of 27 patients with a PD-L1 negative tumor will be included.
• Have at least 2 separate (metastatic) lesions of which one is eligible for irradiation and another for biopsy and RECIST tumor evaluation.
• Demonstrate adequate organ function. All screening labs should be performed within 14 days of treatment initiation.
• Female subject of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the 1st dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
⁃ Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
⁃ Male subjects should agree to use an adequate method of contraception starting with the 1st dose of study therapy through 6 months after the last dose of study therapy