Data from a phase II study of disitamab vedotin (previously known as RC48) shows clinically meaningful results in the treatment of heavily pretreated patients with HER2-expressing advanced or metastatic gastric cancer.

The data were presented at the ASCO20 Virtual Scientific Program organized by the American Society of Clinical Oncology (ASCO), held on May 29-31, 2020.

Disitamab vedotin is a novel humanized anti-HER2 antibody-drug conjugate or ADC developed to treat several HER2 expressing solid tumors. The drug links the potent microtubule inhibitor monomethyl auristatin E (MMAE) to a novel antibody with a higher affinity to HER2 compared to the standard of care. The mechanism of action included inhibition of HER2 signal pathway and cytotoxicity of MMAE, leading to a superior antitumor activity compared to other treatments in animal models.

Disitamab vedotin was the first ADC drug approved for human clinical trials in China and a favorable safety profile has been observed in clinical trials. It is currently being studied in multiple late-stage clinical trials across solid tumor types.

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Jianmin Fang, Ph.D., founder, and Chief Executive Officer of RemeGen. Fang is also the Chairman of MabPlex, an industry leader in biopharmaceutical contract manufacturing.

Clinical progress
“For the third year in a row, we are pleased to showcase clinical progress of [disitamab vedotin] in a broad range of solid tumor treatments at ASCO,” noted Jianmin Fang, Ph.D., founder, and Chief Executive Officer of RemeGen, the developer of the investigational ADC.

“We are encouraged to see positive data from the latest research, and we believe that [disitamab vedotin] has the potential to redefine treatment for patients with HER2-expressing advanced or metastatic gastric cancer,” Fang added.

Study design
This is an open-label, multicenter, single-arm, phase II study. Eligibility criteria include: histologically confirmed gastric or gastro-esophageal junction cancers, HER2-overexpression (IHC 2+ or 3+), ECOG PS 0-1, post-to ≥2 prior systemic treatment. The patients received disitamab vedotin, 2.5 mg/kg, Q2W until disease progression, unacceptable toxicity, withdrawal, or study termination. In this study, the investigators evaluated the primary endpoint ORR, PFS, OS, and safety.

All patients evaluated in the study had received 2 or more lines of chemotherapy treatments with a subgroup of patients having received an additional line of systemic therapy treatment including trastuzumab (Herceptin®; Genentecg/Roche). The study also included patients with low expressing HER2 (IHC2+ / FISH-) tumors, potentially widening the population of patients who may benefit from this therapy.

Study Results
The single-arm Phase II multicenter clinical study conducted in China was designed to evaluate the efficacy and safety of disitamab vedotin. The study enrolled 127 patients (IHC2+ including FISH+ and FISH-, and IHC3+) with advanced or metastatic gastric cancer including gastric or gastroesophageal junction adenocarcinoma.

The median age was 58 years. At baseline, 59 patients (46.5%) had received ≥ 3 lines prior treatments.

The investigator-assessed confirmed objective response rate (ORR) was 18.1% (95% CI: 11.8%, 25.9%). The confirmed sub-group ORR was 19.4% and 16.9% for the patient’s post to 2 lines and ≥ 3 lines, respectively. For 111 patients who were monitored for ≥ 2 cycles of efficacy assessments (i.e. 12 weeks), the ORR was 20.7% (95% CI: 13.6%, 29.5%).

Overall, for the 127 participating patients, the mPFS was 3.8 months (95% CI: 2.7, 4.0, 89 events [70.1%]) and the mOS was The most commonly reported treatment-related AEs were leukopenia (52.0%), alopecia (51.2%), neutropenia (48.0%), and fatigue (42.5%).

Key endpoint
The key endpoint of the study was the objective response rate (ORR) of the main efficacy index evaluated by the independent efficacy evaluation committee (IRC). The confirmed ORR was 23.6%, with a median progression-free survival period (mPFS) of 4.1 months. The median overall survival time (mOS) was 7.6 months (95% CI: 6.6, 9.2, 52 events [40.9%]).

The results of the study demonstrate disitamab vedotin’s potential in addressing the urgent unmet medical need for this heavily treated patient population.

Clinical trial
A Study of RC48-ADC in Local Advanced or Metastatic Gastric Cancer Subjects With the Overexpression of HER2 – NCT03556345

Reference
Peng Z, Liu T, Wei J, Wang A, He Y, Yang L, Zhang X, Fan NF, Luo S, et al. A phase II study of efficacy and safety of RC48-ADC in patients with locally advanced or metastatic HER2-overexpressing gastric or gastroesophageal junction cancers. J Clin Oncol 38: 2020 (suppl; Abstr 4560); 10.1200/JCO.2020.38.15_suppl.4560.