A randomized trial of TLR-2 agonist CADI-05 targeting desmocollin-3 for advanced non-small-cell lung cancer.
Randomized controlled trial to evaluate synergy between taxane plus platinum chemotherapy and CADI-05, a Toll like receptor-2 agonist targeting desmocollin-3 as a first-line therapy in advanced non-small-cell lung cancer (NSCLC).



Patients with advanced NSCLC (stage IIIB or IV) were randomized to cisplatin-paclitaxel (chemotherapy group, N = 112) or cisplatin-paclitaxel plus CADI-05 (chemoimmunotherapy group, N = 109). CADI-05 was administered a week before chemotherapy and on days 8 and 15 of each cycle and every month subsequently for 12 months or disease progression. Overall survival was compared using a log-rank test. Computed tomography was carried out at baseline, end of two cycles and four cycles. Response rate was evaluated using Response Evaluation Criteria in Solid Tumors criteria by an independent radiologist.



As per intention-to-treat analysis, no survival benefit was observed between two groups [208 versus 196 days; hazard ratio, 0.86; 95% confidence interval (CI) 0.63-1.19; P = 0.3804]. In a subgroup analysis, improvement in median survival by 127 days was observed in squamous NSCC with chemoimmunotherapy (hazard ratio, 0.55; 95% CI 0.32-0.95; P = 0.046). In patients receiving planned four cycles of chemotherapy, there was improved median overall survival by 66 days (299 versus 233 days; hazard ratio, 0.64; 95% CI 0.41 to 0.98; P = 0.04) in the chemoimmunotherapy group compared with the chemotherapy group. This was associated with the improved survival by 17.48% at the end of 1 year, in the chemoimmunotherapy group. Systemic adverse events were identical in both the groups.



There was no survival benefit with the addition of CADI-05 to the combination of cisplatin-paclitaxel in patients with advanced NSCLC; however, the squamous cell subset did demonstrate a survival advantage.
Department of Medical Oncology, Penn State Milton S, Hershey Medical Center, Penn State Hershey Cancer Institute, Hershey, USA.
C P
CP
Belani
Department of Research and Development, Cadila Pharmaceuticals Ltd, Ahmedabad, India.
B C
BC
Chakraborty
Department of Research and Development, Cadila Pharmaceuticals Ltd, Ahmedabad, India.
R I
RI
Modi
Department of Research and Development, Cadila Pharmaceuticals Ltd, Ahmedabad, India.
B M
BM
Khamar
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D051187:Desmocollins / Q000037:antagonists & inhibitors; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D051195:Toll-Like Receptor 2 / Q000819:agonists; D016896:Treatment Outcome
D001428:Bacterial Vaccines; C490356:DSC3 protein, human; D051187:Desmocollins; C000625648:Immuvac; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D017239:Paclitaxel; D002945:Cisplatin
TLR agonist; chemoimmunotherapy; desmocollin-3; non-small-cell lung cancer; squamous non-small-cell lung cancer