Uliledlimab/Toripalimab Combo Demonstrates Efficacy and Safety in Advanced NSCLC

Uliledlimab in combination with toripalimab generated notable response rates in patients with advanced non–small cell lung cancer who were previously ineligible to receive standard-of-care treatment.

The differentiated CD73 antibody uliledlimab (TJ004309) in combination with toripalimab (Tuoyi) generated notable response rates in patients with advanced non–small cell lung cancer (NSCLC) who were previously ineligible to receive standard-of-care treatment, according to data from an ongoing phase 2 trial (NCT04322006).1

At a data cutoff of March 29, 2022, a cohort of patients with advanced NSCLC who were ineligible for standard treatment (n = 19) achieved an overall response rate (ORR) of 26%. Five patients achieved a partial response (PR) and 9 patients had stable disease. The disease control rate in this cohort was 73.7%.

Notably, 2 other cohorts of heavily pretreated patients with advanced NSCLC showed a lower clinical response.

“The data represent a step forward for patients with advanced NSCLC. To date, uliledlimab has shown a favorable safety profile and positive antitumor activity in patients with lung cancer, particularly in those patients with a higher baseline CD73 expression,” principal investigator Yi-Long Wu, MD, professor of Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, and Guangdong Lung Cancer Institute in Guangzhou, China, said in a press release. “While the study is ongoing and we are analyzing the data as they mature, we are extremely encouraged by these results and the clinical benefits that uliledlimab may offer to patients.”

Uliledlimab is a differentiated, humanized antibody against CD73 that is hypothesized to deliver clinical benefit by suppressing tumor growth in combination with checkpoint inhibitor therapies, such as PD-1/PD-L1 antibodies.

Previous data from the phase 1 dose escalation study demonstrated favorable safety, pharmacokinetics, and pharmacodynamics for uliledlimab with or without atezolizumab (Tecentriq).2 The agent was well tolerated up to 30 mg/kg administered every 3 weeks, the highest dose explored in phase 1, and investigators observed no dose-limiting toxicities. In heavily pretreated patients with various cancers, the ORR was 23%, and the disease control rate was 46%. The recommended phase 2 dose was established at 20 mg/kg every 3 weeks.

The phase 1/2 study enrolled adults with histologically or cytologically confirmed unresectable or metastatic solid tumors who experienced disease progression on or intolerance to standard treatment or for which there are no effective treatments available.3 Patients were also required to have an ECOG performance status of 0 or 1.

Additional data showed that, among those ineligible for standard-of-care therapy, 80% of patients in the NSCLC cohort of presented with low PD-L1 expression at baseline, classified as a tumor proportion score of 1% to 49% or less than 1%. In this cohort, 4 of 5 patients with high CD73 expression, defined as at least 35% expression in tumor cells or immune cells, achieved a PR. Investigators observed high CD73 expression 4 of 9 patients who had stable disease. None of the remaining 5 patients who progressed on treatment had high CD73 expression.

Investigators plan to expand the phase 2 study to focus on the selected NSCLC cohort for treatment efficacy, and to clarify the role of CD73 as a potentially predictive biomarker.

Investigators hope to launch a phase 3 trial in patients with NSCLC in 2023 if approved by the China National Medical Products Administration. Additionally, another clinical trial is expected to be launched in the United States evaluating uliledlimab in combination with other anti–PD-1/PD-L1 therapies in other select cancer types in the next year.

“The latest data readout, although preliminary, gives hope to those lung cancer patients who often do not benefit from the currently available treatments,” Andrew Zhu, MD, PhD, president of I-Mab, said in a press release. “We are excited by uliledlimab’s potential as a best-in-class CD73 antibody and the clinical results obtained so far have given us the confidence for further clinical development towards registration. We look forward to accelerating our clinical development plan in China and the United States with the goal to initiate a registrational clinical study soon.”


  1. I-Mab reports latest phase 2 clinical data of its differentiated CD73 antibody uliledlimab. News release. I-Mab. May 26, 2022. Accessed May 26, 2022.
  2. Robert F, Dumbrava EE, Xing Y, et al. Preliminary safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of uliledlimab (TJ004309), a differentiated CD73 antibody, in combination with atezolizumab in patients with advanced cancer. J Clin Oncol. 2021;39(suppl 15):2511-2511. doi:10.1200/JCO.2021.39.15_suppl.2511
  3. A phase I/II study of TJ004309 for advanced solid tumor. ClinicalTrials.gov. Updated April 15, 2022. Accessed May 26, 2022. https://www.clinicaltrials.gov/ct2/show/NCT04322006