Sintilimab Shows Progression-Free Survival Benefit in Front-line NSCLC

"The emergence of the anti-PD-1 antibody has brought a new treatment modality for patients with squamous NSCLC."

The IgG4 monoclonal antibody, sintilimab (Tyvyt), in combination with gemcitabine and platinum chemotherapy prolonged progression-free survival (PFS) in first-line advanced or metastatic squamous non–small cell lung cancer (NSCLC), meeting the primary end point of the phase III ORIENT-12 trial, Innovent Biologics announced in a press release.1

“The emergence of the anti–PD-1 antibody has brought a new treatment modality for patients with squamous NSCLC. We are delighted to see that Tyvyt in combination with gemcitabine and platinum chemotherapy has met the predefined primary end point in the ORIENT-12 study. Different from the KEYNOTE-407 study in a different chemotherapy regimen, ORIENT-12 has demonstrated for the first time significant PFS benefit with a PD-1 inhibitor in combination with gemcitabine and platinum in first-line squamous NSCLC,” said Caicun Zhou, MD, PhD, head of the Department of Oncology, Shanghai Pulmonary Hospital, in a statement.

The PFS observed with the sintilimab combination was longer than the PFS seen in patients who received placebo plus gemcitabine and platinum chemotherapy, a difference that was determined by the study investigators to be statistically significant. In addition, sintilimab presented a safety profile that was consistent with prior studies. No new safety signals were reported. The full data from ORIENT-12 will be presented at an upcoming medical conference.

ORIENT-12 is a randomized, double-blind, phase III study to evaluating the safety and efficacy of sintilimab or placebo plus gemcitabine, and platinum chemotherapy in Chinese patients with squamous NSCLC. The study enrollment target is 357 patients, who will be randomized in a 1:1 ratio to receive 200 mg of sintilimab injection or matched placebo in combination with 4 to 6 cycles of gemcitabine for injection plus platinum administered every 3 weeks. Treatment is continued in both study arms until radiographic disease progression, unacceptable toxicity, or any other conditions that require treatment discontinuation; although conditional crossover to the experimental arm is also permitted. Initial treatment is followed by sintilimab or placebo maintenance therapy.

The primary end point of PFS was assessed by independent radiographic review committee; secondary end points of the study include overall survival and safety.

“Currently, we have several phase III randomized clinical trials ongoing in lung cancer. With the encouraging result of ORIENT-12, we are hopeful that sintilimab has the potential to benefit more patients with squamous NSCLC. For Innovent, this is the second randomized study of NSCLC that met its primary endpoint; the first was ORIENT-11, a randomized phase III study of first-line non-squamous NSCLC,” Hui Zhou, vice president and head of Oncology Strategy and Medical Sciences of Innovent, stated in the press release.

Sintilimab is also showing promise in other settings of NSCLC, including patients with advanced or recurrent non-squamous NSCLC within sensitizing EGFR mutation or ALK rearrangement. The ongoing phase III ORIENT-11 (NCT03607539) also met its predefined primary end point of PFS versus placebo. Results from the interim analysis of ORIENT-11 are also expected to be presented at an upcoming medical meeting.2

A total of 397 participants are expected to enroll in ORIENT-11. Patients with adanced or recurrent squamous NSCLC will be randomized 2:1 to receive 200 mg sintilimab plus up to 4 cycles of chemotherapy, every 3 weeks.

Based on results from interim results from the ORIENT-11 trial, a New Drug Application was submitted to the National Medical Products Administration in China for sintilimab in combination with pemetrexed and platinum chemotherapy as first-line treatment for nonsquamous NSCLC. Experts believe that ORIENT-12 will further prove the potential of sintilimab in the treatment landscape of NSCLC.1


1. Tyvyt (sintilimab injection) combined with Gemzar (gemcitabine for injection) and platinum chemotherapy met the predefined primary endpoint in the phase 3 orient-12 study as first-line therapy in patients with locally advanced or metastatic squamous non-small cell lung cancer [news release]. Suzhou, China: Innovent Biologics, Inc; May 6, 2020. Accessed May 7, 2020.

2. Tyvyt (sintilimab injection) combined with Alimta (pemetrexed) and platinum met predefined primary endpoint in phase 3 orient-11 study as first-line therapy in nonsquamous nsclc [news release]. Suzhou, China: Innovent Biologics, Inc; January 12, 2020. Accessed May 7, 2020.