Introduction

The human innate immune system plays a pivotal role in detecting cancer-induced DNA damage and signaling the adaptive immune system to initiate an anti-tumor immune response. However, many cancer cells develop mechanisms to evade immunosurveillance. IMSA101 is a STING Agonist that augments the detection/signaling role via the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway. When IMSA101 is combined with DNA-damage inducing personalized ultra-fractionated stereotactic adaptive radiation therapy (PULSAR), given monthly and an Immune Checkpoint Inhibitor (ICI), we hypothesize a synergy will be formed that will optimize the immune system response. The IMSA101 Phase II program will evaluate the combination of PULSAR-ICI with/without IMSA101 for the treatment of oligometastatic and oligoprogressive metastatic solid tumors. The primary endpoint will compare progression-free rates for patients in a control group (PULSAR-ICI only) versus experimental group (PULSAR-ICI-IMSA101). 

Methods

IMSA101-102 is a phase 2, open-label, multicenter randomized clinical trial comparing the safety and efficacy of PULSAR and ICI with or without IMSA101 in patients with oligometastatic non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). The study will start by enrolling approximately 9 patients to an ascending dose level, safety lead-in period where all patients will receive PULSAR + ICI + IMSA101 at either 800mcg or 1200mcg IMSA101 dose levels. Once the safety lead-in period is complete, approximately 34 patients will be randomized in a 1:1 ratio to either the experimental group (PULSAR + ICI + IMSA101) or to the control group (PULSAR + ICI).

IMSA101-103 is a phase 2, open-label, multicenter randomized clinical trial comparing the safety and efficacy of PULSAR + with or without IMSA101 in patients with oligoprogressive solid tumor malignancies. The study will start by enrolling approximately 9 patients to an ascending dose level, safety lead-in period where all patients will receive PULSAR + ICI + IMSA101 at either 800mcg or 1200mcg IMSA101 dose levels. Once the safety lead-in period is complete, approximately 39 patients will be randomized in a 2:1 ratio to either the experimental group (PULSAR + ICI + IMSA101) or to the control group (PULSAR + ICI) respectively.

In both trials, the treatment regimen will consist of: 1) three doses of PULSAR, spaced 1 month apart, 2) either Nivolumab or Pembrolizumab ICI dosed according to product label and, for patients in the experimental group, 3) five intra-tumoral injections of IMSA101 over a 60-day period. All patients will be assessed for anti-tumor efficacy at screening, prior to the end Cycle 3, and at 8-week intervals thereafter based on radiographic assessments and analysis of ORR, DOR, TTP, and PFS (all outcome measures per RECIST Version 1.1 and iRECIST). A Quality of Life Assessment will be performed using the FACT-G tool which measures four domains of health related QoL, namely physical, social, emotional, and functional well-being, in cancer patients.

Results

To be provided at later date, pending enrollment and data collection.

Conclusion

The goal of the two Ph 2 trials is to determine if the triplet therapy of IMSA101 + PULSAR + ICI provides a greater proportion of patients remaining progression-free after commencement of therapy than those patients receiving PULSAR + ICI alone.