Abstract 70MO
Background
Envafolimab (KN035) is a novel anti-PD-L1 single domain antibody formulated for subcutaneous injection (SC). This single arm phase II study evaluated the efficacy and safety of KN035 in patients (pts) with advanced microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) cancer.
Methods
The study included adult pts with MSI-H/dMMR advanced cancer who failed ≥ 1 line of systemic therapy in China. Pts received SC administration of KN035 at 150 mg weekly until progression, unacceptable toxicity, or withdrawal. The primary endpoint was ORR per RECIST v1.1 by blinded independent radiology review (BIRC).
Results
As of 2019/12/5, 103 pts with dMMR/MSI-H advanced cancer were enrolled, including 65 with colorectal cancer (CRC, 41 failed ≥ 2 lines of prior therapies including a fluoropyrimidine (F), oxaliplatin (O) and irinotecan (I), 24 failed 1 line of prior therapy including F, O or I), 18 with gastric cancer (GC) and 20 with other tumors. As of data cut off on 2020/6/19, the median follow-up was 11.5 months in the overall population. Confirmed ORR per BIRC was 42.7% in the overall population, 43.1% in CRC, 44.4% in GC and 40.0% in other tumors population. Median duration of response was not reached for any populations. ORRs per investigators were consistent with BIRC assessment (Table). Table: 70MO
Confirmed ORR per BIRC and investigator assessment
| ORR per BIRC | ORR per investigator | |
| Overall population (n=103) | 42.7% (95%CI: 33.0%-52.8%) | 41.7% (95% CI: 32.1%-51.9%) |
| CRC population (n=65) | 43.1% (95% CI: 30.8%-56.0%) | 40.0% (95% CI: 28.0%-52.9%) |
| CRC failed prior 1 line (n=24) | 62.5% (95%CI: 40.6%-81.2%) | 58.3% (95% CI: 36.6%-77.9%) |
| CRC failed prior ≥2 lines (n=41) | 31.7% (95%CI: 18.1%-48.1%) | 29.3% (95% CI: 16.1%-45.5%) |
| GC population (n=18) | 44.4% (95%CI: 21.5%-69.2%) | 50.0% (95% CI: 26.0%-74.0%) |
| Other tumors population (n=20) | 40.0% (95%CI: 19.1%-63.9%) | 40.0% (95% CI: 19.1%-63.9%) |
The median progression-free survival (PFS) per BIRC was 7.2 months for CRC population, not reached for either GC or other tumors population, and 11.1 months for the overall population. Median overall survival (OS) was not reached for any populations. The 12 months OS rate was 72.9%, 83.3%, 75.0% and 74.6% for CRC, GC, other tumors, and overall population, respectively. All grade (G) and G3-4 treatment-related adverse events (TRAE) in overall population were 84.5% and 15.5% separately. No G5 TRAE occurred. The most common immune related AEs were hypothyroidism (15.5%) and hyperthyroidism (11.7%). No pneumonitis or colitis were reported. The occurrence of local injection-site reaction was 8.7% and were all G1-2.
Conclusions
Envafolimab demonstrated robust anti-tumor activity with a manageable safety profile in heavily pretreated pts with dMMR/MSI-H cancer.
Clinical trial identification
NCT03667170.
Editorial acknowledgement
Legal entity responsible for the study
3DMedicine Co. Ltd.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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