Daiichi and AstraZeneca’s Antibody Drug Conjugate

ESMO 2021 Preview: Daiichi and AstraZeneca’s Antibody Drug Conjugate (ADC) in advanced NSCLC

The entrance of antibody-drug conjugates (ADCs) in the cancer space is not much older, and since then, they have been in use so widely that today we have more than ten ADCs approved now and more than 100 in the current clinical pipeline. As ADCs are the new targeting platforms in oncology, many pharma giants have signed billion-dollar deals just to grasp the specific subset of the indication. One such deal was signed between Daiichi Sankyo and AstraZeneca, which are co-developing datopotamab deruxtecan (DS-1062), one of three lead DXd ADCs in the oncology pipeline of the company after Trastuzumab deruxtecan and Patritumab deruxtecan. The drug is being explored in different indications such as NSCLC, TNBC, and hormone receptor-positive breast cancer. The company is all set to present the data from its phase I study (TROPION-PanTumor01) of DS-1062 in patients with NSCLC at ESMO 2021 following the dose analysis study presented at ASCO 2021 from the same cohort.

The efficacy of the drug in the phase I study is going to be presented under the late-breaking abstracts, which suggest its explored potential through its interim trial results.

The interim results published in January 2021 showed promising clinical activity for datopotamab deruxtecan in patients with advanced or metastatic NSCLC. ORR ranging from 21–25% was observed in 159 patients with NSCLC receiving different doses of the drug (4mg/kg, 6mg/kg, or 8mg/kg). Thirty-two confirmed complete or partial responses. Efficacy data were preliminary due to immaturity of follow-up across dose groups, but preliminary efficacy results may support the durability of clinical activity. A DCR ranging from 67–80% was observed with a median PFS ranging from 4.3–8.2 months across the three doses of datopotamab deruxtecan. The most common Grade 3 or greater TEAEs included mucosal inflammation, anemia, stomatitis, and fatigue.

The late-breaking presentation (Abstract LBA49) is expected to highlight promising results from a sub-group analysis of the patients with advanced/metastatic NSCLC and actionable genomic alterations in solid tumors. The results from the phase I trial are much awaited as based on the efficacy and safety findings, the recommended dose will be identified for the registrational TROPION-Lung01 (phase III trial), which is evaluating DS-1062 against docetaxel in previously treated advanced/metastatic NSCLC without actionable genomic alterations.

Expert Opinion: “These updated preliminary results from TROPION-PanTumor01 are encouraging, as responses were seen across all three doses of the drug, underscoring the potential of targeting TROP2 with an antibody-drug conjugate in advanced or metastatic NSCLC. We look forward to seeing the results from the Phase III trial, which will further evaluate datopotamab deruxtecan versus chemotherapy.”

– Virginia Cancer Specialists, US Oncology Research

Not only with datopotamab deruxtecan, Daiichi is also optimistic with its other ADCs at ESMO 2021 medical conference. The company is also unveiling new data from its phase II study evaluating trastuzumab deruxtecan in patients with HER2-mutated metastatic NSCLC (DESTINY-Lung01). The preliminary analysis from the study showed a confirmed ORR of 24.5%, with a DCR of 69.4% and median OS of 11.3 months. The additional primary study results will be released under the late-breaking abstracts (LBA45) at ESMO 2021, which are eagerly awaited. Not just in NSCLC, trastuzumab deruxtecan data readouts in other indications such as breast cancer, colorectal cancer, and others can be further assessed at ESMO 2021.

Talking about other ADCs from Daiichi Sankyo, DS-7300 is an investigational B7-H3 targeting agent, which is in phase I for solid tumours, and the company is planning to present the preliminary data from the study. Another competitor Macrogenics, is going to present the preliminary results from its phase I study in advanced solid tumors evaluating MGC018, another anti-B7-H3 ADC. Let’s now see what ESMO 2021 has for ADC platform holders and how vivid we can remain with the ADCs where we already know that these assets are already packed with black box warnings issuing toxicities within the patients.

* Non-small cell lung cancer (NSCLC), Triple-negative breast cancer (TNBC), Objective response rate (ORR), Disease control rate (DCR), Progression-free survival (PFS), Treatment-emergent adverse events (TEAEs), Antibody-drug conjugates (ADCs)