Sintilimab Shows Promising Response Rates in Advanced NSCLC Patients with High Mutation Burden

Sintilimab Shows Promising Response Rates in Advanced NSCLC Patients with High Mutation Burden

Treatment with sintilimab, Innovent‘s PD-1 inhibitor, induces high response rates in non-small cell lung cancer (NSCLC) patients who have failed at least one prior treatment, particularly in those with a high number of mutations in their tumor cells, results from a Phase 1b clinical trial show.

The findings were presented recently at the 2018 Annual Meeting of Chinese Society of Clinical Oncology (CSCO), in Beijing, China.

Sintilimab (IBI308), a human anti-PD-1 antibody developed by Innovent and Eli Lilly, works by preventing PD-1 on immune cells from binding to PD-L1 at the surface of cancer cells. This interaction tells immune cells to leave cancer cells unharmed, and blocking it restores T-cells’ ability to recognize and destroy cancer cells.

The antibody showed a potent anti-tumor activity in preclinical models, leading researchers to conduct a Phase 1b trial evaluating its safety and preliminary effectiveness in patients with advanced solid tumors.

The trial was composed of two parts. In Phase 1a, researchers explored four doses and regimens of sintilimab — 1mg/kg, 3mg/kg or 10mg/kg intravenous every two weeks, or 200mg intravenous every three weeks — in multiple advanced solid tumors. The main goal of this part was to determine the best sintilimab dose to be given to patients for further testing.

Among the 12 patients who received at least one dose of the medicine, two patients — one with liver cancer and another with a neuroendocrine tumor — experienced a partial reduction in their tumors, which lasted 9.5 and 5.7 months, respectively.

Fever, thyroid dysfunction, elevation of liver enzymes, and lung inflammation were the most common treatment-related side effects, and the 200mg dose, given every three weeks was chosen for further examinations.

In the Phase 1b part of the study, patients were recruited into four separate groups: patients with advanced melanoma, patients with advanced disease of the digestive system who had failed at least one prior therapy, NSCLC patients who also had failed at least one prior line of treatment, and finally, patients with locally advanced non-squamous NSCLC with an inoperable tumor.

All received sintilimab alone, except for the last group of patients, which received the medicine in combination with the chemotherapies Platinol (cisplatin) and Alimta (pemetrexed).

Researchers have now reported data from the third group, those with NSCLC receiving sintilimab as a stand-alone agent, showing that 17.6% of the 34 patients examined achieved at least a partial tumor reduction. These patients lived without their disease progressing for a median of 2.8 months and their median overall survival was of 13.8 months.

For the six patients with a high tumor mutation burden, however, responses were even more striking – half the patients responded to the treatment and the other half saw their disease stabilize.

The figures are comparable to those seen in patients with advanced NSCLC and high tumor mutation burden treated with two immune checkpoint inhibitors like sintilimab — Opdivo (nivolumab) and Yervoy (ipilimumab), and higher than those for chemotherapy.

The incidence and severity of side effects was similar to other PD-1 inhibitors, researchers reported.

“As a physician, it is our relentless pursuit to explore safer and more effective treatments to help the patient with malignant tumors to obtain a healthier and longer life,” Li Zhang, professor at the Sun Yat-Sen University Cancer Center, said in a press release. “We have great expectations for sintilimab and hope to see more positive results in the future clinical trials, which will benefit more patients and families soon.”

Innovent is now assessing the effectiveness of sintilimab in a larger, randomized trial, which is testing the medicine against the chemotherapy Taxotere (docetaxel) in advanced or metastatic NSCLC patients who progressed during first-line platinum-based chemotherapy. The Phase 3 trial, called ORIENT-3 (NCT03150875), is recruiting up to 266 patients in China.

“At present, the phase III study of the second line squamous NSCLC is progressing smoothly, and we hope to provide more treatment options for lung cancer patients in the future,” added Michael Yu, Founder, CEO and chairman of Innovent.