2186P - KN046 in patients with thymic carcinoma: A prospective, single-arm, multi-centre, phase II study

Background

Thymic carcinoma (TC) is a rare but highly aggressive cancer, with no standard treatment for patients who progress after platinum-containing chemotherapy.KN046 is a novel bispecific antibody that inhibits both PD-L1/PD1 and CTLA-4/CD80/CD86 pathways. We conducted this phase 2 study aiming to evaluate the efficacy and safety of KN046 in the TC patients who progressed after front-line chemotherapy.

Methods

Patients documented with histologically TC who progressed after platinum-containing chemotherapy were eligible. KN046 was injected intravenously at 5mg/kg Q2W until tumor progression or unacceptable toxicity. The primary endpoint was ORR by IRC, and secondary endpoints were DoR, PFS, OS, and safety. Response was assessed every 8 weeks. PD-L1 expression was measured using 22C3 PharmDx assay.

Results

From Dec 2020 to Dec 2022, 46 patients were enrolled into the study with a median age of 58 (range:38-69) years. There was no difference in gender distribution (male: female=25:21). 22 patients received more than one line of systemic chemotherapy. Most patients (91.3%) had stage IVB disease, ECOG PS was 0 in 10 (21.7%) and 1 in 36 (78.3%) patients, respectively. 17 patients had positve PD-L1, 25 patients had negative PD-L1 and 4 patients were unknown. The median follow-up time was 16.1 months (ranges:11.1-18.6 months). Of 38 evaluable patients, 7 achieved partial response and 17 remained stable disease, while the other 14 experienced progressive disease. The ORR was 16.3% (95%CI: 6.8%, 30.7%), the mDoR was 10.1 months (95%CI: 7.7, NE). The mPFS was 5.6 months (95%CI: 1.9, 12.8). The mOS was immature, the 18-months OS rate was 74.1% (95%CI: 54.29, 86.32). Among the PD-L1-positive patients, the ORR and PFS were numerically higher than that in PD-L1 negative or status unknown, which was 18.8% vs. 14.8% in ORR and 7.6 months vs 5.6 months in PFS. The most common TRAE of any grade include rash (39.1%), ALT increased (32.6%), AST increased (28.3%). 8 patients experienced ≥ grade 3 irAE, 7 (15.2%) patients discontinued study treatment due to TRAE, but there was no death event related with KN046.

Conclusions

KN046 demonstrated promising antitumor activity and acceptable toxicity in thymic carcinoma patients who have received at least one line of chemotherapy.

Clinical trial identification

NCT04469725.

Editorial acknowledgement

Legal entity responsible for the study

Alphamab Oncology.

Funding

Alphamab Oncology.

Disclosure

All authors have declared no conflicts of interest.