Combination Therapy Shows Significant Response Rates in Advanced NSCLC

Combination therapy with uliledlimab (TJ004309) plus toripalimab (Tuoyi) produced significant response rates in patients with advanced non–small cell lung cancer (NSCLC) previously ineligible to receive standard-of-care treatment, according to data from an ongoing phase 2 trial (NCT04322006) presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

At the data cutoff of March 29, 2022, patients with advanced NSCLC who were ineligible for standard treatment (n = 19) administered the combination therapy achieved an overall response rate (ORR) of 26%, 5 patients achieved a partial response (PR), and 9 had stable disease. The disease control rate in this group of patients was 73.7%.

Additionally, 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, a differentiated, humanized antibody against CD73, is believed to produce a clinical benefit by suppressing tumor growth in combination with checkpoint inhibitor therapies, such as PD-1/PD-L1 antibodies, according to the study investigators.

Prior findings from a phase 1 dose escalation study showed favorable safety, pharmacokinetics, and pharmacodynamics for uliledlimab with or without atezolizumab (Tecentriq).²

Uliledlimab was found to be well tolerated at up to 30 mg/kg administered every 3 weeks, which was the highest dose explored in phase 1. There were no dose-limiting toxicities observed in this portion of the study. Among heavily pretreated patients with various cancers, 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 adult patients with histologically or cytologically confirmed unresectable or metastatic solid tumors with disease progression on, or intolerance to, standard treatment or for which there are no approved effective treatments.³ Enrollees were required to have an ECOG performance status of 0 or 1.

The study found that among patients ineligible for standard-of-care therapy, 80% in the NSCLC portion of the trial presented with low PD-L1 expression at baseline, classified as a tumor proportion score of 1% to 49% or less than 1%.

In this group, 4 of 5 patients with high CD73 expression, defined as at least 35% expression in tumor cells or immune cells, achieved a PR. High CD73 expression was observed in 4 of 9 patients who had stable disease and zero of the other 5 patients who progressed on treatment had high CD73 expression.

The phase 2 study will next be expanded to analyze the selected NSCLC group for treatment efficacy and to clarify the role of CD73 as a potentially predictive biomarker.

“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.”

References

1. I-Mab reports latest phase 2 clinical data of its differentiated CD73 antibody uliledlimab. News release. I-Mab. May 26, 2022. https://www.prnewswire.com/news-releases/i-mab-reports-latest-phase-2-clinical-data-of-its-differentiated-cd73-antibody-uliledlimab-301555755.html
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