Collaboration to Study Antibody Drug, Keytruda in Lung Cancer

Daiichi Sankyo and AstraZeneca recently entered into a second clinical trial collaboration and supply agreement with Merck to evaluate an antibody-drug conjugate with Keytruda in patients with non-small cell lung cancer (NSCLC). 

The global Phase 3 TROPION-Lung08 trial will evaluate datopotamab deruxtecan, a TROP2 directed DXd antibody-drug conjugate, and Merck’s Keytruda compared to Keytruda alone in patients with PD-L1 high advanced or metastatic NSCLC without genomic alterations. 

“In this specific trial, we will evaluate whether combining our TROP2 directed ADC with an anti-PD-1 therapy improves outcomes in patients with previously untreated advanced non-small cell lung cancer with no actionable genomic alterations,” said Gilles Gallant, BPharm, PhD, FOPQ, senior vice president and global head of oncology research & development at Daiichi Sankyo. 

Lung cancer is the second most common cancer and the leading cause of cancer-related mortality globally, with 80 to 85 percent classified as NSCLC. 

NSCLC generally has a poor prognosis with worsening outcomes after each line of subsequent therapy. The current standard of care in the first-line treatment of patients with metastatic NSCLC is PD-L1 immunotherapy with or without platinum-based chemotherapy.  

But nearly 40 to 60 percent of tumors do not respond to initial treatment and disease progression occurs. Therefore, new innovative treatment approaches are crucial. 

Daiichi Sankyo, AstraZeneca, and Merck entered into their first trial collaboration agreement in May 2020 for the TROPION-Lung02 Phase 1b trial evaluating the safety and efficacy of datopotamab deruxtecan and Keytruda with or without platinum-based chemotherapy. 

In six study cohorts, researchers studied two dose levels of datopotamab deruxtecan, 4.0 milligrams/ kilograms and 6.0 milligrams/kilogram, combined with 200 milligrams of Keytruda.

The companies launched a second clinical trial collaboration based on the positive results from the TROPION-Lung02 ongoing trial. 

“While PD-L1 immunotherapy can improve outcomes in advanced or metastatic non-small cell lung cancer, the progression-free survival for the majority of patients is still less than one year,” said Cristian Massacesi, MD, chief medical officer and oncology chief development officer at AstraZeneca. 

“The TROPIONLung08 trial will evaluate whether the combination of datopotamab deruxtecan and an immune checkpoint inhibitor that targets the PD-1 pathway will improve outcomes in this setting,” Massacesi concluded.