Innovent Biologics, Inc. presented the Phase 1 clinical data of its first-in-class PD-1/IL-2a bispecific antibody fusion protein (R&D code: IBI363) in advanced solid tumors at the 2024 ASCO Annual Meeting (ClinicalTrials.gov, NCT05460767). More updated data from the Phase 1 study including in non-small cell lung cancer will be presented orally at the European Society for Medical Oncology (ESMO) Virtual Plenary later this month. Phase 1 Study of PD-1/IL-2a (IBI363) in Melanoma, Colorectal Cancer and Other Solid Tumors: This Phase 1a/1b study was conducted to evaluate the safety, tolerability and preliminary efficacy of IBI363 in subjects with advanced solid tumors.

For melanoma cohort (abstract#: 9562): 67 subjects with locally advanced or metastatic melanoma who failed or intolerant to standard treatment were enrolled and received IBI363 intravenously at dose levels between 100 µg/kg QW and 2 mg/kg Q3W. 89.6% of subjects had received prior immunotherapy, and 61.2% of subjects had = 2 lines of prior systemic therapy. 25.4% of subjects had baseline liver metastasis and 70.1% of subjects were acral or mucosal subtypes.

As of January 11, 2024, 57 subjects had at least 1 post-baseline tumor assessment. The best overall response was complete response (CR) in 1 subject, partial response (PR) in 15 subjects respectively. The overall response rate (ORR) was 28.1% (95%CI: 17.0-41.5) and DCR was 71.9% (95%CI: 58.5-83.0).

In 25 immunotherapy (IO) treated subjects in 1mg/kg Q2W dose group (n=25), the ORR was 32.0% (95%CI: 14.9-53.5), DCR was 80.0% (95%CI: 59.3-93.2). As for safety, 16 (23.9%) subjects had grade =3 treatment emergent adverse events (TEAEs). Most common TEAEs were arthralgia (34.3%), hyperthyroidism (29.9%), and anemia (25.4%).

Grade =3 immune related adverse events (irAEs) occurred in 8 (11.9%) subjects. No TRAE leading to death occurred. For colorectal cancer cohort (abstract#: 3593): 68 subjects with locally advanced or metastatic colorectal cancer who failed or intolerant to standard treatment were enrolled and received IBI363 intravenously at dose levels between 100 µg/kg QW and 3 mg/kg Q3W.

There were 83.8% subjects with microsatellite stable (MSS)/proficient mismatch repair (pMMR), and the MMR status of the others were unknown. 76.5% of the subjects had previously received = 3rd line system therapy, and 61.8% of subjects had liver metastases at baseline. As of December 22, 2023, median follow-up time was 5.3 (95% CI: 4.4-6.9) months.

The best overall response was complete response (CR) in 1 subject, partial response (PR) in 7 subjects respectively. The overall ORR was 12.7% (95%CI: 5.6-23.5). The ORR of the 1 mg/kg dose group was 15.0% (95% CI: 3.2-37.9).

In 13 subjects with PD-L1 CPS =1, ORR was 30.8% (95%CI: 9.1-61.4), DCR was 76.9% (95%CI: 46.2-95.0). As for safety, grade =3 treatment emergent adverse events (TEAEs) occurred in 22 (32.4%) subjects. Most common TEAEs were arthralgia (35.3%), anemia (32.4%), pyrexia (22.1%) and hypoalbuminemia (20.6%).

Grade =3 immune related adverse events (irAEs) occurred in 4 (5.9%) subjects. No TRAE leading to death occurred. For other tumors (abstract#:e14593): As of January 26, 2024, 13 subjects with biliary tract cancers (BTC), 3 subjects with head and neck squamous cell carcinoma (HNSCC), 4 subjects with cervical cancer (CC) and 4 subjects with ovarian cancer (OC) received IBI363 monotherapy.

In 11 evaluable patients with BTC, 1 patient (IO-failed) had confirmed partial response (cPR), 9 patients (including 6 patients with tumor regression) had stable disease (SD) and 1 patient had progressive disease (PD). In 2 evaluable patients with HNSCC, 1 patient had cPR (IO-naïve, PD-L1 expression negative) and 1 patient had PD. In 3 evaluable patients with CC, 1 patient had cPR (IO-failed), 1 patient had SD and 1 patient had PD.

In 2 evaluable patients with OC, 1 patient had cPR (platinum-resistant) and 1 patient had PD. In 4 patients with cPR, 3 patients still on treatment and 1 patient with HNSCC received curative resection.