INSPIRE Study - AIM with Immunotherapy - Immuno-Oncology Essentials

INSPIRE Study

Study Goal: To evaluate the performance of the ctDNA detection platform for prognostication and response monitoring
Subjects: 94 patients with advanced or metastatic solid tumors treated with pembrolizumab
Tumor types included: head-and-neck squamous-cell carcinoma, triple-negative breast cancer, ovarian cancer, and melanoma
Patients received a median of 3 pembrolizumab cycles
Results:
- ctDNA concentration correlated with progression-free survival, overall survival, clinical response, and clinical benefit. ctDNA kinetics also correlated with outcomes: all 12 patients with negative ctDNA during treatment were alive with median 25 months follow-up (see Figure A)

Figure A. Kaplan-Meier curve showing overall survival in subjects who cleared, had a decrease from baseline, or had an increase from baseline in ctDNA. Reprinted with permission from Bratman SV et al. Nature Cancer. 2020:1:873-881.

The test also identifies treatment nonresponders with a 100% positive predictive value. A rising ctDNA and progressive disease on imaging predicted treatment nonresponse with 100% accuracy. See Figure B for overall survival rates for different risk groups defined by both ctDNA responses and response criteria based on imaging.

Figure B. Overall survival rates based on ctDNA and response criteria based on imaging. Reprinted with permission from Bratman SV et al. Nature Cancer. 2020:1:873-881. C3 = cycle 3; CR = complete response; SD = stable disease; PD = progressive disease.