Tyvyt Effective, Safe in Previously Treated Patients with Hodgkin’s Lymphoma, Phase 2 Trial Shows

Treatment with Tyvyt (sintilimab injection) was found safe and eased the tumor burden or led to cancer disappearance in nearly 3 out of 10 patients with relapsed or refractory classical Hodgkin’s lymphoma, according to follow-up results of a Phase 2 clinical trial in China.

Trial findings, “Sintilimab for relapsed/refractory classical Hodgkin’s lymphoma: Extended follow-up on the multicenter, single-arm phase II ORIENT-1 study,” were presented at the recent 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Tyvyt, developed jointly by Innovent Biologics and Eli Lilly and Company, is a type of antibody therapy called an immune checkpoint inhibitor. It boosts anti-cancer responses by binding to the PD-1 protein on T-cells and blocking their interaction with PD-L1 on cancer cells.

The multicenter ORIENT-1 trial (NCT03114683) tested the efficacy and safety of Tyvyt in patients with relapsed or refractory classical Hodgkin’s lymphoma. It included 96 participants who failed to respond to two or more lines of systemic therapy, including an autologous stem cell transplant.

The primary goal was objective response rate (ORR), which refers to the proportion of patients achieving a predetermined reduction in tumor burden. Tyvyt was given intravenously (into the vein) at 200 mg every three weeks.

As of the data cutoff on Oct. 16, 2018, 72.9% of patients were still being treated over a median follow-up of 14 months and 20 treatment cycles (range 1 to 26).

The ORR was 85.4%. Twenty-eight patients (29.2%) achieved a complete response, as assessed by positron emission tomography (PET) scan. Among the 82 patients with complete or partial responses, 59 were still responding to the therapy. As a result, the median duration of response and progression free survival — the length of time without disease worsening — had not yet been reached.

As for safety, the most frequent treatment-related adverse event as fever (40.6%), with most cases (92.3%) being mild or moderate. The most common severe or life-threatening adverse events related to treatment were fever (3.1%) and anemia (3.1%). One patient died, but this was deemed not related to treatment.

The positive ORIENT-1 results have led to the approval of Tyvyt in China for patients with classical Hodgkin’s lymphoma who failed to respond or experienced a relapse after two or more prior lines of chemotherapy. Data from this trial were recently published and showed a favorable comparison with Opdivo (nivolumab) and Keytruda (pembrolizumab), two other approved immune checkpoint inhibitors.

“In addition to a high rate of response,” Tyvyt “also demonstrated durable efficacy and favorable long-term safety profile after extended follow-up,” the researchers wrote, also mentioning that ORIENT-1 had the largest group of classical Hodgkin’s lymphoma patients treated with a PD-1 therapy in China.

According to a press release, Innovent presented results from other studies, including the Phase 2 ORIENT-4 trial (NCT03228836), at the ASCO meeting on the treatment of relapsed or refractory extranodal NK/T-cell lymphoma with Tyvyt.

The presentation, “Sintilimab for relapsed/refractory (r/r) extranodal NK/T cell lymphoma (ENKTL): A multicenter, single-arm, phase 2 trial (ORIENT-4),” showed that two-thirds of patients responded to treatment with Tyvyt, even after failing a median of three prior lines of therapy. A total of 85.7% of patients benefited from the treatment, achieving either disease stabilization or a reduction in tumor burden.

Importantly, while these patients usually live less than six months after failing prior treatment with L-asparaginase, 82% of patients in ORIENT-4 were alive after one year, suggesting Tyvyt “could be a promising treatment option for these patients,” the researchers wrote.