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618 Phase 1 clinical trial evaluating the safety, biologic and anti-tumor activity of the novel STING agonist IMSA101 administered both as monotherapy and in combination with PD-(L)1 checkpoint inhibitors
  1. Justin C Moser1,
  2. Angela Alistar2,
  3. Ezra Cohen3,
  4. Edward Garmey4,
  5. Syed Kazmi5,
  6. Teresa Mooneyham6,
  7. Lijun Sun6,
  8. Timothy Yap7 and
  9. Devalingam Mahalingam8
  1. 1HonorHealth Research Instittue, Scottsdale, AZ, USA
  2. 2Atlantic Health System, Morristown, NJ, USA
  3. 3University of California San Diego, La Jolla, CA, USA
  4. 4ImmunSensor, Dallas, TX, USA
  5. 5UT Southwestern, Dallas, TX, USA
  6. 6ImmuneSensor, Dallas, TX, USA
  7. 7The University of Texas, Houston, TX, USA
  8. 8Northwestern University, Chicago, IL, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Anti-tumor efficacy of immuno-oncology (IO) approaches remains limited to a minority of tumor subtypes and considerable efforts remain focused on strategies to improve IO activity in immune-refractory or ‘cold’ tumors. A recently discovered innate immunity pathway, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), plays a critical role in anti-tumor immunity. IMSA101 is a small molecule analogue of cGAMP that directly activates STING with high potency. Pre-clinical studies demonstrate provocative anti-cancer activity both with IMSA alone and in combination with ICI and radiotherapy.

Methods IMSA101–101 (NCT# 04020185) is a first-in-human phase 1 trial evaluating IMSA101 both as monotherapy and in combination with ICIs at 6 U.S. cancer centers. The study’s primary objective was to identify recommended phase 2 doses of IMSA101. Patients (pts.) ≥ 18 yrs. with locally advanced or metastatic solid tumor malignancies were administered intra-tumoral IMSA at escalating dose levels (100–1200 mcg.) weekly (with cycle 1) and bi-weekly thereafter. For the combination cohort, ICI naiive pts. or those with initial disease progression through ICI monotherapy were administered IMSA101 at escalating dose levels beginning at the monotherapy RP2D -1.

Results 22 pts. were enrolled across 5 monotherapy dose cohorts with no dose-limiting toxicities (DLTs) or drug-related serious adverse events (SAEs) observed. 31 study-drug related TEAEs were reported in 14 pts. (63.6%). IMSA101 appeared well-absorbed and distributed with Tmax of 0.7 hrs and t1/2 of 1.8 hrs. Both Cmax/AUC and cytokine levels increased in a dose proportional manner. In the combination cohort, 18 pts. were enrolled in 3 dose cohorts ranging from 800–2400 mcg. with a total of 23 TEAEs reported in 11 pts. (61.1%). A single Grade 1 TEAE of cytokine release syndrome (CRS) was reported at 800 mcg. and this resolved 1 day after onset. One pt. (1200 mcg.) experienced a DLT of G3 arthropathy. Based on PK/safety findings, 1200 mcg. was selected as the RP2D of IMSA101 for both mono and combination therapy. While no formal RECIST-based responses were observed in monotherapy, notable tumor regressions were observed in both injected and non-injected lesions. In the combination arm, a single and ongoing PR (66%) was observed in a pt. with refractory uveal melanoma.

Conclusions Intra-tumoral administered IMSA101 is safe and well tolerated. Notable efficacy signals with both monotherapy and in combination with ICI were observed. Phase 2 randomized trials evaluating the combination of IMSA101, ICI and pulsed radiotherapy (PULSAR) in the settings of oligometastatic and oligo-progressive disease are now underway.

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