The first patient has been dosed in a phase I study assessing the safety and tolerability of DS-1062, an investigational trophoblast cell-surface antigen 2 or TROP2-targeting antibody-drug conjugate or ADC, in patients with unresectable advanced non-small cell lung cancer (NSCLC) who are refractory to or have relapsed following standard treatment or for whom no standard treatment is available.[1]

The novel agent is being developed by Japanese drug-maker Daiichi Sankyo. It’s the third ADC in clinical development based on Daiichi Sankyo’s proprietary linker and payload technology.


With the initiation of this study … Daiichi Sankyo moves a third Antibody-drug Conjugate into the clinic …  investigating the potential of the smart delivery of chemotherapeutic agents in various cancers including lung, breast and gastric cancer.


Antibody-drug conjugates are targeted cancer medicines that deliver cytotoxic chemotherapeutic payload to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

MabPlex
 

Proprietary ADC technology
Designed using Daiichi Sankyo’s proprietary ADC technology, DS-1062 is a smart chemotherapy comprised of a humanized anti-TROP2 monoclonal antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

Trial design
The phase I, open-label study is a first-in-human study investigates the safety and tolerability of DS-1062 in patients with unresectable advanced NSCLC who are refractory to or have relapsed following standard treatment or for whom no standard treatment is available.

The first part of the study, know as the dose escalation phase, assesses the safety and tolerability of increasing doses of DS-1062 to determine the maximum tolerated dose and recommended dose for expansion. The second part of the study (dose expansion) will evaluate the safety and tolerability of DS-1062 at the recommended dose for expansion.

Study endpoints include safety, pharmacokinetics, objective response rate, duration of response, disease control rate, time to response, progression-free survival, overall survival, biomarker analysis and immunogenicity. This portion of the study is expected to enroll approximately 40 patients with unresectable advanced NSCLC in the United States and Japan.

Following the outcome of both the dose escalation and dose expansion parts of the study in patients with unresectable advanced NSCLC, there may be two additional expansion cohorts opened for other solid tumors where high expression of TROP2 is frequently observed.

Improved patient outcome
With the discovery of driver genes and introduction of targeted therapies, there has been improvement in patient outcomes for certain types of NSCLC. However, for patients with unresectable advanced NSCLC, there is still a need for new therapeutic strategies as the five-year survival rates for patients with advanced stages of NSCLC are low.[2]

DS-1062 is designed to target and deliver chemotherapy inside cancer cells expressing trophoblast cell-surface antigen 2 (TROP2), which is overexpressed in many cancers including NSCLC.[3] Overexpression of TROP2 is a driver in cancer growth and has been associated with decreased patient survival, increased tumor aggressiveness, metastasis, and drug resistance in several tumor types.[4]

“We are initially focusing on evaluating DS-1062 in patients with advanced NSCLC with potential expansion into other tumor types depending on the results of this early critical test in a study designed to provide evidence supporting unique properties of this particular TROP2 ADC construct,” noted Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo.

“With the initiation of this study of DS-1062, we move our third ADC into the clinic and continue to investigate the potential of the smart delivery of chemotherapy in various cancers including lung, breast and gastric cancer,” Yver concluded.