"Breast cancer treatments received positive reviews"

new drugs from global pharma show potential

Padcev, targeting nectin-4, shown to be effective in treating triple-negative breast cancer

Positive results obtained with datopotamab·sacituzumab tirumotecan

Major antibody-drug conjugates (ADC) have secured positive clinical results in treating breast cancer.

 

ADCs under development by global pharmaceutical companies have shown to be effective in various types of breast cancer, including triple-negative breast cancer, hormone-positive (HR+)/HER2-negative breast cancer.

 

With these results, latecomers have established a foundation to secure indications for breast cancer, following the cases of Kadcyla, Enhertu, and Trodelvy.

 

According to industry sources on June 4th, clinical achievements of several ADCs, including Padcev, datopotamab deruxtecan, and sacituzumab tirumotecan, were presented at the American Society of Clinical Oncology (ASCO 2024) annual meeting, which started on May 31st.

 

Astellas and Seagen have presented clinical outcomes of their ADC Padcev.

 

Padcev, an ADC anticancer agent targeting the cell surface protein nectin-4, has been approved worldwide for urothelial carcinoma.

 

During this meeting, the results of the phase 2 EV-202 clinical study, confirming its potential in breast cancer, were disclosed.

 

Both companies are exploring possibilities not only in urothelial carcinoma but also in breast cancer, gastric cancer, and non-small cell lung cancer, as nectin-4 protein is expressed in various solid tumors.

 

On June 2, the Phase 2 study results of Padcev, a nectin-4-targeting ADC, were presented at ASCO 2024 (source: snapshot of ASCO 2024 lecture presentation).

EV-202 clinical study evaluated Padcev’s effectiveness and safety in patients with triple-negative breast cancer and hormone (HR) positive·HER2-negative breast cancer who have been treated with chemotherapy before.

 

The primary endpoint was objective response rate (ORR), and the secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and and safety/drug tolerance.

 

The clinical results showed that the Padcev treatment group had an ORR of 19.0% for triple-negative breast cancer, while the DRR, an index measuring the percentage of patients with no disease progression during or after the treatment, was 57.1%.

 

Such results were consistent with the outcomes for HR+/HER2- breast cancer.

 

The Padcev treatment group recorded an ORR of 15.6%, while the DCR was 51.1%.

 

The treatment-related adverse events (TRAE) of over Grade 3 for Padcev were decreased neutrophil counts (7%), decreased white blood cell counts (5%), and increased aspartate aminotransferase (5%).

 

Adverse reactions identified in two cohorts were manageable and consistent with previously disclosed safety data.

 

Currently, for triple-negative breast cancer, there is no ADC approved after Trodevly.

 

All eyes are on whether Padcev would secure an indication for treating triple-negative breast cancer through follow-up clinical results.

 

A TROP2-targeting ADC demonstrated additional effects on breast cancer On June 2, the clinical results of datopotamab deruxtecan, under development by Daiichi Sankyo and AstraZeneca, and MSD’s sacituzumab tirumotecan were disclosed.

 

These two drugs are ADCs targeting TROP2 protein, an intracellular calcium signal transducer regulating cell proliferation and survival.

 

TROP2 protein is expressed in healthy cells but commonly overexpressed in cancer cells.

 

The protein is also associated with drug resistance.

 

Gilead Sciences’ Trodelvy is the only available drug with a similar mechanism that succeeded in commercialization.

 

Datopotamab is under clinical trials to confirm its potential for breast cancer and non-small cell lung cancer.

 

The TROPION-BREAST01 study showed that datopotamab improved PFS for HR+/HER2- breast cancer.

 

This time, the report detailing the study’s patient reported outcome (PRO) was disclosed.

 

The TROPION-BREAST01 study increased the likelihood of datopotamab securing an indication to treat breast cancer (source: snapshot of ASCO 2024 lecture presentation).

The clinical study involved 732 patients with inoperable or metastatic HR+/HER2- breast cancer previously treated with at least one chemotherapy.

 

The patients were randomly assigned to either the datopotamab group or investigator’s choice of chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) with a 1:1 allocation.

 

The PRO included (GGS), quality of life (QoL), and time to deterioration (TTD) evaluated by EORTC QLQ-C30, a questionnaire to assess the quality of life of cancer patients.

 

The clinical results showed that the TTD for QOL in the datopotamab group was 3.4 months, compared to 2.1 months in the chemotherapy group.

 

TTD for the datopotamab group was confirmed to be delayed in terms of physical function, pain, and most other symptoms and functioning scales.

 

MSD’s sacituzumab tirumotecan was shown to be effective in triple-negative breast cancer.

 

In 2022, MSD licensed the ADC candidate sacituzumab from China-based Sichuan Kelun-Biotech.

 

Results from the phase 3 OptiTROP-Breast01 study compared sacituzumab to investigator’s choice chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with locally recurrent or metastatic breast cancer.

 

The primary endpoint was PFS, assessed by blinded independent central review (BICR).

 

Interim analysis results for PFS showed that the sacituzumab group recorded a PFS of 5.7 months, which was longer than the 2.3 months in the chemotherapy group.

 

PFS at 6 months was 43.4% for the sacituzumab group and 11.1% for the chemotherapy group.

 

Sacituzumab reduced the disease progression and mortality risk by 69%.

 

OS was significantly favorable for Sacituzumab treatment.

 

“Sacituzumab monotherapy demonstrated clinically meaningful PFS and OS benefits compared to chemotherapies,” an investigator stated.

 

“Moreover, it demonstrated a manageable safety profile for treating triple-negative breast cancer, which has limited treatment options.”