FDA Grants Fast Track Designation to IBI363 for Squamous NSCLC

The FDA has granted fast track designation to the first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein IBI363 for the treatment of patients with unresectable, locally advanced, or metastatic squamous non–small cell lung cancer (NSCLC) that has progressed following anti–PD-(L)1 therapy and platinum-based chemotherapy.1

Data from a phase 1 trial (NCT05460767) presented at the 2024 IASLC World Conference on Lung Cancer demonstrated that patients with squamous NSCLC who had received previous immunotherapy and were treated with a 3-mg/kg dose of IBI363 (n = 18) achieved an objective response rate (ORR) of 50.0% and a disease control rate (DCR) of 88.9%. At a minimum of 12 weeks of follow-up for this group, the median progression-free survival (PFS) was not reached.

At a 1.0-mg/kg or 1.5-mg/kg dose, the median PFS was 5.5 months (95% CI, 1.5-8.3), and the 12-month PFS rate was 30.7%.

Across dose levels of 1.0 mg/kg, 1.5 mg/kg, and 3.0 mg/kg, the ORRs were 36.4% for patients with a PD-L1 tumor proportion score (TPS) of less than 1% (n = 22) and 31.8% for patients with a PD-L1 TPS of at least 1% (n = 22).

“We are pleased that IBI363 has been granted fast track designation by the FDA for squamous NSCLC, following its previous designation for melanoma. Earlier, we reported that in an expanded cohort of [patients with] squamous NSCLC, IBI363 showed a trend toward improved ORR and DCR at higher doses, along with a manageable safety profile,” Hui Zhou, PhD, senior vice president of Innovent Biologics, stated in a news release. “The latest PFS data from the 3-mg/kg dose group after longer follow-up further strengthens our confidence in IBI363’s potential as an immunotherapy offering long-term benefits to patients. We will present the relevant data at upcoming academic conferences [in 2025].”

The ongoing phase 1 study is evaluating the bispecific antibody in patients with advanced solid tumors or lymphoma.2 Investigators are enrolling patients at least 18 years of age with histologically or cytologically confirmed, unresectable, locally advanced or metastatic solid tumors or lymphomas who experienced disease progression or were intolerant to standard therapy, or did not have standard therapy available. Notably, prior treatment and progression on a PD-1/L1 inhibitor is permitted.

Other key inclusion criteria consist of at least 1 measurable lesion per RECIST 1.1 criteria for solid tumors or Lugano 2014 criteria for lymphomas; an ECOG performance status of 0 or 1; and a life expectancy of at least 3 months.

Patients are being excluded if they have a history of or known active seizure disorders, brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease; active thrombosis or a history of deep vein thrombosis or pulmonary embolism within 4 weeks of first study drug unless adequately treated and considered stable by investigator assessment; active uncontrolled bleeding or a known bleeding diathesis; and massive pleural effusion or ascites.

All patients are receiving IBI363 in at various dose levels with the goal of determining the maximum tolerated dose and the recommended phase 2 dose.

The incidence of dose-limiting toxicities and safety are serving as the trial’s primary end points. Secondary end points include pharmacokinetics, ORR, time to response, duration of response, DCR, PFS, and overall survival.

Safety data reported at the 2024 IASLC World Conference on Lung Cancer showed the most common treatment-related adverse effects (TRAEs) included arthralgia, anemia, hyperthyroidism, hypothyroidism and rash.3 Grade 3 or higher TRAEs occurred in 20.1% of patients, and TRAEs led to treatment discontinuation in 6.0% of patients.

At the 3-mg/kg dose (n = 57), the rates of grade 3 or higher TRAEs and TRAEs leading to treatment discontinuation were 17.5% and 5.3%, respectively.

“More encouragingly, IBI363 has demonstrated potent antitumor activity regardless of PD-L1 expression levels. This suggests that IBI363 may not only advance treatment for immunotherapy-resistant populations but also for cold tumors with low or no PD-L1 expression,” Zhou added in the news release.1 “In addition to lung cancer, we have observed encouraging efficacy signals in cold tumors, including colorectal cancer and mucosal melanoma, with [IBI363 in] melanoma already advancing to pivotal clinical stages. Moving forward, we will continue to explore IBI363 in early-line treatment and in combination therapies.”

References

1. Innovent receives second fast track designation from the U.S. FDA for IBI363 (PD-1/IL-2α-bias bispecific antibody fusion protein) in squamous non-small cell lung cancer. News release. Innovent Biologics. February 17, 2025. Accessed February 17, 2025. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=508
2. Safety, tolerability and preliminary efficacy of IBI363 in subjects with advanced solid tumors or lymphoma. ClinicalTrials.gov. Updated December 29, 2023. Accessed February 17, 2025. https://clinicaltrials.gov/study/NCT05460767
3. Innovent delivers oral presentation on phase 1 clinical data of IBI363 (first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) in advanced non-small cell lung cancer at the 2024 WCLC. News release. Innovent Biologics. September 10, 2024. Accessed February 17, 2025. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=482