FDA Fast-Tracks IBI363 in Squamous NSCLC

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

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

The agent is being evaluated in a phase 1 trial (NCT05460767) for patients with squamous NSCLC. Data presented at the 2024 IASLC World Conference on Lung Cancer showed that among the patients given prior immunotherapy and treated with a 3-mg/kg dose of IBI363 (n = 18), the objective response rate (ORR) was 50.0%. In this group, the disease control rate (DCR) was 88.9%.²

With a minimum follow-up of 12 weeks for this cohort, the median progression-free survival (PFS) had not yet been reached. For patients receiving doses of 1.0 mg/kg or 1.5 mg/kg, the median PFS was 5.5 months (95% CI, 1.5-8.3), with a 12-month PFS rate of 30.7%.

Among patients treated at dose levels of 1.0 mg/kg, 1.5 mg/kg, and 3.0 mg/kg, the overall response rates (ORRs) were 36.4% in those with a PD-L1 tumor proportion score (TPS) below 1% (n = 22) and 31.8% in those with a PD-L1 TPS of 1% or higher (n = 22).

3D rendered medical illustration of male anatomy with lung cancer: ©Sebastian Kaulitzki - stock.adobe.com

“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, said in a press release.¹ “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 this year.”

According to safety findings from the trial, the most common treatment-related adverse events (TRAEs) seen in patients were arthralgia, anemia, hyperthyroidism, hypothyroidism and rash.² TRAEs deemed grade 3 or higher were observed in 20.1% of patients. Further, TRAEs led to treatment discontinuation in 6.0% of patients enrolled in the study.

Among the 57 patients treated with the 3-mg/kg dose of IBI363, grade 3 or higher TRAEs were seen in 17.5% of patients and TRAEs led to treatment discontinuation in 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,” added Zhou in the press 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.”

About the Phase 1 Study of IBI363

In the ongoing, open-label, multicenter, phase 1 study of IBI363, investigators are assessing the safety, tolerability, and preliminary efficacy of the bispecific antibody when used for the treatment of patients 18 years and older with advanced solid tumors or lymphoma.³ The trial is ongoing in China.

Enrollment in the trial is open to patients with histologically or cytologically confirmed, unresectable, locally advanced or metastatic solid tumors or lymphomas. Patients must have experienced disease progression, must have been intolerant to standard therapy, or did not have standard therapy available. Patients are required to have an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, at least 1 measurable lesion per RECIST 1.1 criteria for solid tumors or Lugano 2014 criteria for lymphomas. Moreover, patients are eligible for enrollment if they had received previous treatment and progression on a PD-1/L1 inhibitor.

IBI363 is being given to all patients enrolled in the study at various dose levels. The main goal of the study is to determine the maximum tolerated dose and the recommended phase 2 dose of IBI363.

The primary end points of the study are to determine the incidence of dose-limiting toxicities and safety of IBI363. Secondary end points consist of ORR, time to response, duration of response, DCR, PFS, overall survival, and pharmacokinetics.

In September 2024, the FDA granted a fast track designation to IBI363 for the treatment of patients with unresectable locally advanced or metastatic melanoma that has progressed following at least 1 line of systemic therapy, including a PD-(L)1 inhibitor.⁴

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 18, 2025. https://tinyurl.com/2c68348x

2. 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 18, 2025. https://tinyurl.com/fxnky82t

3. Safety, tolerability and preliminary efficacy of IBI363 in subjects with advanced solid tumors or lymphoma. ClinicalTrials.gov. Updated December 29, 2023. Accessed February 18, 2025. https://clinicaltrials.gov/study/NCT05460767

4. Innovent receives fast track designation from the U.S. FDA for IBI363 (PD-1/IL-2α bispecific antibody fusion protein) as monotherapy for advanced melanoma. News release. Innovent Biologics. September 3, 2024. Accessed February 18, 2025. https://tinyurl.com/2p9e4xz6