Abstract 1028P
Background
In NSCLC, combining blockade of PD-1 and CTLA-4 is more effective than monotherapy but is accompanied by an increase in toxicity. Thus, it is of great interest to identify patients who benefit from adding the CTLA-4 inihibitor to the anti-PD-1 therapy in case of progression. We present data from the NSCLC cohort of the BIOLUMA trial, which evaluates efficacy and safety of nivolumab and ipilimumab in lung cancer and includes a translational program to identify potential biomarkers predictive of response and resistance.
Methods
BIOLUMA is an investigator-initiated, multicentre, phase II trial in 2nd line patients with non-squamous NSCLC. Patients are treated with nivolumab 240 mg until disease progression (part A) and subsequently with a combination therapy of nivolumab 3 mg/kg q2w and ipilimumab 1mg/kg q6w (part B). Primary endpoint is overall response rate of the combination treatment. Analysis of sequential tumor biopsies and PBMCs were performed at different timepoints.
Results
In total, 27 patients were enrolled. Two patients dropped out due to changes of tumor histology after central pathological assessment. Thirteen patients were transferred to treatment part B (combination therapy nivolumab plus ipilimumab) and were available for primary endpoint analysis. In 4 of these patients (30.8%) the addition of ipilimumab induced a tumor response: three patients with primary nivolumab refractory disease experienced partial response (2 confirmed by RECIST). One patient had an unconfirmed SD after addition of ipilimumab. PD occured in 9 out of 13 patients. The cohort was terminated early due to a high dropout rate of 52% from treatment part A to B, mainly attributed to rapid disease progression and immune-mediated adverse event while on nivolumab treatment.
Conclusions
In nivolumab refractory NSCLC patients, addition of ipilimumab shows promising anti-tumor activity. The results give an important signal for further trials in 1st line setting for overcoming resistance to anti-PD-1 monotherapy by sequentially adding a second checkpoint inhibitor and hereby moving potential toxicity and chemotherapy to later treatment lines.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Lung Cancer Group Cologne.
Funding
Bristol Myers Squibb.
Disclosure
R.N. Fischer: Financial Interests, Personal and Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Roche, AstraZeneca. J.K. Kern: Financial Interests, Personal, Invited Speaker: Roche, Sanofi, Boehringer Ingelheim, MSD, BMS/Celgene, Lilly, Takeda, Novartis, AstraZeneca, Pfizer; Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim, MSD, BMS/Celgene, Lilly, Takeda, Novartis, AstraZeneca, Pfizer; Financial Interests, Personal, Other: Roche, Sanofi, Boehringer Ingelheim, MSD, BMS/Celgene, Lilly, Takeda, Novartis, AstraZeneca, Pfizer. J. Panse: Financial Interests, Personal, Advisory Board: Alexion, Amgen, Apellis, AstraZeneca, Blueprint Medicines, Bristo-Myers Squibb, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, Sobi; Financial Interests, Personal, Invited Speaker: Alexion, Apellis, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, MSD, Neopharm Israel, Novartis, Pfizer, Roche, Sobi, SwixxBiopharma. M. Sebastian: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Johnson, Lilly, Merck, MSD, Novartis, Takeda; Financial Interests, Personal, Invited Speaker: GSK, Roche; Financial Interests, Personal, Research Grant: AstraZeneca. M. Serke: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol-Myers Squibb, MSC, Roche, Celgene; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol-Myers Squibb, MSC, Roche, Celgene. L. Nogova: Financial Interests, Personal, Invited Speaker: Pfizer, Celgene, Novartis, Roche, Boehringer Ingelheim, Bristol-Myers Squibb, Takeda, Bayer, Janssen, AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis, Boehringer Ingelheim, Bristol-Myers Squibb, Roche, Janssen, Pfizer, Takeda, Bayer, AstraZeneca; Financial Interests, Institutional, Research Grant: Pfizer, Bristol-Myers Squibb, Novartis, MSD, Janssen, Amgen, Dracen; Financial Interests, Personal, Other: Novartis, Pfizer, Celgene, Boehringer Ingelheim, Janssen. J. Weber: Financial Interests, Personal, Invited Speaker: Lilly, Amgen, Merck. R. Büttner: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Illumina, Lilly, Merck-Serono, MSD, Novartis, Qiagen, Pfizer, Roche, Targos MP Inc; Financial Interests, Personal, Ownership Interest: Targos Mol. Pathology Inc; Financial Interests, Personal, Member of the Board of Directors: Gnothis Inc; Financial Interests, Personal, Advisory Role: MSD. J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Ignyta, Janssen, Loxo, MSD, Pfizer, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Blueprint, Chugai, Daiichi Sankyo, Lilly, Novartis, Roche, Seattle Genetics; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, Janssen Pharmaceutica, Novartis, Pfizer. All other authors have declared no conflicts of interest.