Tyvyt, PD-1 Inhibitor Newly Approved in China, Showed Efficacy Similar to Opdivo and Keytruda, Trial Data Show

Tyvyt, PD-1 Inhibitor Newly Approved in China, Showed Efficacy Similar to Opdivo and Keytruda, Trial Data Show

The immune checkpoint inhibitor Tyvyt (sintilimab injection) reduced tumor burden in eight out of 10 people with relapsed or refractory classic Hodgkin’s lymphoma taking part in a Phase 2 clinical trial in China, researchers report. Responses were also durable, with 77% of these patients reaching the six-month mark without signs of disease worsening.

These findings compare favorably with those seen in Phase 2 trials of Opdivo (nivolumab) and Keytruda (pembrolizumab) — two approved immune checkpoint inhibitors for Hodgkin’s lymphoma patients who failed prior therapies — and were the basis for Tyvyt’s recent approval in China.

Full data from the ORIENT-1 Phase 2 trial (NCT03114683) were recently published in the journal Lancet Haematologyin the study “Safety and activity of sintilimab in patients with relapsed or refractory classical Hodgkin lymphoma (ORIENT-1): a multicentre, single-arm, phase 2 trial.”

Treatment with PD-1 inhibitors, like Opdivo and Keytruda, has led to clinical responses in classical Hodgkin’s lymphoma patients who do not respond to prior therapies, and is usually given after patients fail with Adcetris (brentuximab vedotin) and an autologous stem cell transplant.

In China, however, Adcetris is not approved and stem cell transplants are often not affordable, leaving chemotherapy as the only option for relapsed or refractory classical Hodgkin’s lymphoma patients.

The ORIENT-1 study was designed to test if Tyvyt, another PD-1 inhibitor jointly developed by Innovent Biologics and Eli Lilly and Company in China, could be used in these patients.

It included 92 patients in China, who received a Tyvyt infusion every three weeks for up to two years, or until disease worsening,  unacceptable toxicity, study withdrawal, or death. Nearly all patients (96%) had undergone a stem cell transplant and more than half (54.2%) had received radiotherapy.

After a median follow-up of 10.5 months, 74 patients (80.4%) had an objective response, defined as a complete or partial remission of the tumor seen in imaging scans. In 34% of cases, the tumor disappeared.

Among those who responded, 77% achieved a response within six weeks, and 20% within 24 weeks. Two other patients achieved partial remission at weeks 36 and 48.

At the time of the analysis, no one had died, and 77.6% reached the six-month mark with no signs of disease worsening. The data was similar to that of the Opdivo and Keytruda trials, where 77% and 69% of patients had a similar outcome.

“Treatment with sintilimab, as reported in this trial, results in response rates very similar to those of other PD-1 antibodies as well as similar durability of benefit,” Stephen M. Ansell, editor-in-chief of Lancet Haematology, said in an editorial comment accompanying the study.

Interestingly, response rates remained unchanged regardless of the number of prior lines of chemotherapy, history of radiotherapy, and history of stem cell transplant.

The most frequent treatment-related adverse event was fever, detected in 41% of patients. Most reported side effects were mild or moderate.

“In China, there are no approved PD-1 monoclonal antibodies for patients with relapsed or refractory classical Hodgkin lymphoma, and the unmet medical need for this population is huge. Sintilimab could be a new treatment option for these patients,” the researchers wrote.

“Sintilimab is likely to be available in parts of the world where current anti-PD-1 antibodies are not available, making a highly effective treatment modality (immune checkpoint blockade) available to more patients and potentially improving the outcomes of patients with classical Hodgkin lymphoma worldwide,” Ansell added.

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