AZ and Daiichi’s TROP2 ADC shows promise in first-line lung cancer

by Stephen Riddle

Two years after AstraZeneca splashed out $1 billion upfront for rights to Daiichi Sankyo’s TROP2-targeting antibody-drug conjugate DS-1062, the drug has generate promising results in advanced non-small cell lung cancer (NSCLC).

Data from the TROPION-Lung02 reported at the World Congress on Lung Cancer (WCLC) showed an overall response rate of 37% when DS-1062 (datopotamab deruxtecan) was combined with Merck & Co’s PD-1 inhibitor Keytruda (pembrolizumab) , rising to 41% when chemotherapy was added in as well.

The phase 1b trial is investigating the ADC and Keytruda – with or without chemo – in both previously-untreated and pretreated patients with advanced NSCLC who don’t have genetic mutations that would warrant targeted therapies.

As a first-line therapy, DS-1062/Keytruda had an ORR of 62%, compared to 50% with triple therapy with chemo, with a disease control rate (DCR) or 100% and 90%, respectively. In the second-line setting, dual therapy had an ORR of 24%, and 29% with triple therapy.

The results suggest that AZ and Daiichi Sankyo could be in line for a second big win for a cancer ADC to follow Enhertu (trastuzumab deruxtecan), their HER2-directed drug which has just claimed a key FDA approval in HER2-low breast cancer.

It also fires another shot across the bows of Gilead Sciences, whose ADC Trodelvy (sacituzumab govitecan) became the first TROP2-directed drug to be approved for marketing, getting the nod from the FDA as a treatment for triple-negative breast cancer.

Gilead is also testing its drug as a first-line therapy for NSCLC in combination with Keytruda in a trial sponsored by Merck.

AZ licensed rights to DS-1062 in July 2020 for $1 billion upfront – paid over two years – plus up to $5 billion in regulatory and sales milestones. With the positive phase 1b trial in hand, the two partners are now planning a phase 3 trial, called Tropion-Lung08, to further evaluate the DS-1062/Keytruda combination as a first-line combination treatment for NSCLC.

Patritumab deruxtecan starts phase 3

Daiichi Sankyo meanwhile has started a phase 3 trial of another ADC partnered with AZ – patritumab deruxtecan – comparing the drug to chemotherapy as a second-line therapy for EGFR-mutated advanced non-squamous NSCLC.

The HER3-directed ADC will be tested in patients whose disease had progressed despite earlier treatment with EGFR inhibitors, including third-generation drugs like AZ’s Tagrisso (osimertinib). It picked up a breakthrough designation from the FDA last December based on phase 1 results in this setting.

Most EGFR-mutated NSCLCs show some level of HER3 expression, but for now there are no HER3 directed therapies approved for NSCLC or any other form of cancer.

The trial – called HERTHENA-Lung02 – will enrol  around 560 patients and is due to generate results in 2024. In 2020, Daiichi Sankyo and AZ agreed to carry out a clinical trial exploring the combination of Tagrisso with patritumab deruxtecan in patients with this form of cancer who have specific EGFR mutations, namely exon 19 deletion or L858R mutation.

This post was originally published on Source Link

You may also like