Clin Cancer Res: Anti-tumor activity and safety of PD-L1 antibody alone or in combination with TIM-3 antibody in MSI-H/dMMR advanced tumors

Immune checkpoint inhibitors show high response rates and lasting clinical benefits in microsatellite instability-high/mismatch repair defect (MSI-H/dMMR) tumors
.

However, about 50%-60% of tumor patients do not respond to a single dose of anti-PD-1/PD-L1 antibody, and about 50% of responders will relapse within 6-12 months

immunity

This is a phase Ib clinical trial aimed at evaluating the anti-PD-L1 antibody LY3300054 single agent or the combined anti-TIM-3 antibody LY3321367 in patients with advanced solid tumors with microsatellite instability-high/mismatch repair defects Tumor activity and safety
.

Recruited 18-year-old patients with advanced solid tumors who had not received anti-PD-1/PD-L1 treatment and had clear microsatellite instability-high/mismatch repair defects, and received LY3300054 as a single agent (single agent group, n=40) or LY3300054+LY3321367 (pre-treatment combination group, n=20) treatment; PD-1/PD-L1 inhibitor-resistant/refractory patients receive combined treatment (drug-resistant/refractory combination group, n =22)
.

The primary endpoint of the combination group is safety and tolerability

A total of 82 patients were recruited, most of which were colorectal cancer (n=39, 47.
6%) or endometrial cancer (n=14, 17.
1%)
.

In the PD-1/PD-L1 inhibitor resistance/refractory combination group, more than 70% of patients had previous treatment lines ≥3

Colorectal cancer

The occurrence of treatment-related adverse reactions in the three treatment groups

The occurrence of treatment-related adverse reactions in the three treatment groups

Twenty-two (55.
0%) patients in the single-agent group had treatment-related adverse reactions (TRAE), of which 2 patients (5.
0%) were TRAE ≥ grade 3; 13 patients (65.
0%) in the combination group had TRAE, 3 Cases (7.
1%) are TRAE ≥ grade 3
.

TRAE occurred in 6 patients (27.

Twenty-two (55.

Treatment response of patients in the three treatment groups

Treatment response of patients in the three treatment groups

13 (32.
5%) and 9 (45.
0%) patients in the single-agent group and PD-1/PD-L1 inhibitor-initial treatment combination group achieved objective remission ; PD-1/PD-L1 inhibitor resistance/ One patient (4.
5%) in the refractory combination group achieved objective remission
.

Thirteen (32.
5%) and 9 (45.
0%) patients in the single-agent group and the PD-1/PD-L1 inhibitor-initial treatment combination group respectively obtained objective remission in the single-agent group and PD-1/PD-L1 inhibitor 13 (32.
5%) and 9 (45.
0%) patients in the initial treatment combination group achieved objective remissions

In summary, LY3300054 single-drug and LY3300054/anti-TIM-3 combination regimen has controllable safety
.

Both treatments showed promising clinical activity in MSI-H/dMMR tumors initially treated with PD-1/PD-L1 inhibitors

Both treatments showed promising clinical activity in MSI-H/dMMR tumors initially treated with PD-1/PD-L1 inhibitors

Original source:

Antoine Hollebecque, et al.

Safety and Antitumor Activity of α-PD -L1 Antibody as Monotherapy or in Combination with α-TIM-3 Antibody in Patients with Microsatellite Instability-High / Mismatch Repair-Deficient Tumors in this message