STING Agonist and Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy in Combination With Checkpoint Inhibition for Patients With Metastatic Kidney Cancer.

To evaluate the impact of combining innate immune system activation (with IMSA101) with antigen release (through SAbR/PULSAR) on limited progressing lesions during ongoing adaptive immune system activation (with maintenance Nivo).

Start Date01 Apr 2025

Sponsor / Collaborator

The University of Texas Southwestern Medical Center

NCT06026254

/ Active, not recruitingPhase 1

Rollover Study to Continue IMSA101 Treatments in Patients With Advanced Treatment-Refractory Malignancies Previously Enrolled in the Phase I/IIA Safety and Efficacy Study of IMSA101

This is a rollover study from parent protocol IMSA101-101 for adult patients with advanced malignancies that were previously receiving IMSA101 and who would continue to receive benefit with study treatment of IMSA101 in combination with an immune checkpoint inhibitor (ICI).

Start Date15 Sep 2023

Sponsor / Collaborator

ImmuneSensor Therapeutics, Inc.

NCT05846659

/ TerminatedPhase 2

Phase 2 Randomized Clinical Trial Comparing the Safety and Efficacy of PULSAR-Integrated Radiotherapy + Pembrolizumab or Nivolumab Administered With or Without STING-Agonist IMSA101 in Patients With Oligoprogressive Solid Tumor Malignancies

Phase 2, open-label, multicenter, randomized study comparing the safety and efficacy of personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) combined with immune checkpoint inhibitor (ICI) immunotherapy (PULSAR-ICI) + IMSA101 and PULSAR-ICI alone in patients with oligoprogressive solid tumor malignancies after prior anti-cancer therapy.

Start Date07 Jul 2023

Sponsor / Collaborator

ImmuneSensor Therapeutics, Inc.

100 Clinical Results associated with IMSA-101

100 Translational Medicine associated with IMSA-101

100 Patents (Medical) associated with IMSA-101

Literatures (Medical) associated with IMSA-101

01 May 2026·CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Integrating STING activation with programmed death-ligand 1 inhibition: Novel approaches for cancer treatment

Review

Author: Bagheri, Vahid ; Arfaei, Reyhaneh ; Kheiri, Farzaneh ; Shirzad, Zahra ; Khorramdelazad, Hossein ; Yaraghi, Pegah ; Kheyri, Abbas ; Boroumand, Armin

Immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1)/PD-L1 blockade, have transformed cancer therapy; however, primary resistance, limited response durability, and heterogeneous clinical outcomes remain significant challenges. The stimulator of interferon genes (STING) pathway, a central regulator of innate-adaptive immune crosstalk, has emerged as a promising yet biologically complex target in cancer immunotherapy. Acute STING activation enhances type I interferon (IFN-I) production, dendritic cell (DC) maturation, and cytotoxic T lymphocyte (CTL) infiltration, whereas sustained or dysregulated signaling can induce PD-L1 expression and promote immunosuppressive programs within the tumor microenvironment. Preclinical studies demonstrate that a rational combination of STING agonists with PD-1/PD-L1 inhibitors can reprogram the tumor microenvironment, enhance antigen presentation, and improve antitumor immune activity in experimental models. In contrast, early-phase clinical trials of STING agonists, including ADU-S100, SYNB1891, IMSA101, and MK-1454, have shown acceptable safety and pathway engagement but generally modest and variable clinical responses, primarily reflected by low objective response rates and limited disease stabilization. These outcomes highlight the context-dependent nature of therapeutic efficacy and the gap between preclinical expectations and current clinical results. This review synthesizes mechanistic, translational, and clinical evidence to critically evaluate both the therapeutic potential and inherent risks of STING/PD-1/PD-L1 combination strategies. We highlight emerging drug delivery platforms, such as nanocarriers, antibody-drug conjugates, and exosome-based systems, as key modulators of efficacy and safety, and emphasize the importance of biomarker-guided approaches for patient stratification and trial optimization. By integrating biological insight with translational feasibility, this review provides a framework for advancing STING-based combination immunotherapy toward more durable and personalized cancer treatment.

01 Jun 2025·Journal for ImmunoTherapy of Cancer

Phase 1 first-in-human dose-escalation study of IMSA101, a novel cyclic di-nucleotide STING agonist, for patients with advanced solid tumor malignancies

Article

Author: Yap, Timothy A ; Sun, Lijun ; Moser, Justin ; Mahalingam, Deva ; Kazmi, Syed ; Vu, Peter ; Mooneyham, Teresa ; Alistar, Angela ; Jacoby, Jay ; Garmey, Edward

Background:

Despite progress in cancer therapeutics, there remains an unmet need for treatment of advanced solid tumors. The cGAS-cGAMP-STING pathway plays a pivotal role in innate antitumor immunity processes. IMSA101 is a small molecule analog of cGAMP and a potent STING agonist. Preclinical studies demonstrate antitumor activity of IMSA101 alone and in combination with immune-checkpoint inhibitors (ICIs).

Methods:

IMSA101-101 was an open-label, multicenter, phase 1 first-in-human dose-escalation study to establish a recommended phase 2 dose (RP2D) of IMSA101 both as monotherapy and in combination with a programmed death ligand 1 (PD-(L)1)-ICI. Secondary objectives were to evaluate safety, tolerability and antitumor activity, and to characterize pharmacokinetics. Adult patients with advanced solid tumors with ≥2 Response Evaluation Criteria in Solid Tumors evaluable lesions, at least one of these suitable for injection, were enrolled. IMSA101 was administered by intratumoral injection with weekly injections for the first 3 weeks, followed by biweekly injections. The dose escalation explored doses of 100–1,200 µg (monotherapy) and 800–2,400 µg (combination therapy with ICI) in a 3+3 design. No formal statistical analysis was planned for this study.

Results:

40 patients (22 monotherapy, 18 combination therapy) received at least one dose of IMSA101. IMSA101 1,200 µg (monotherapy) and 2,400 µg (combination therapy) doses, well-tolerated and associated with signs of antitumor activity, were selected as provisional RP2Ds. The most common IMSA101-related treatment-emergent adverse events (TEAEs) were injection site pain (8 (36.4%)) and fatigue (4 (18.2%)) for monotherapy and chills (3 (16.7%)), injection site pain (2 (11.1%)), and fever (2 (11.1%)) for combination therapy. No clear dose-response relationship between IMSA101 and occurrence of TEAEs was observed. The elimination half-life of plasma IMSA101 was approximately 1.5–2 hours, with no reported plasma accumulation. With monotherapy, no patients achieved complete response (CR) or partial response (PR), so overall response rate (ORR) was not determined; 17 (77.3%) patients had progressive disease (PD) and one patient (4.5%, 400 µg cohort) had stable disease (SD) as best response. With combination therapy, ORR was 5.6%; remaining patients had PD (10 (55.6%)) and SD (2 (11.1%)) as their best response.

Conclusions:

IMSA101 doses of 1,200 µg (monotherapy arm) and 2,400 µg (combination therapy arm) were well tolerated but demonstrated minimal signals of antitumor activity in patients with advanced solid tumors.

Trial registration number:

NCT04020185.

Nature Communications

The STING agonist IMSA101 enhances chimeric antigen receptor T cell function by inducing IL-18 secretion

Article

Author: Young, Regina M ; Castelli, Sofia ; Assenmacher, Charles-Antoine ; Finck, Amanda V ; June, Carl H ; Uslu, Ugur ; Chen, Zhijian J ; Sun, Lijun

Abstract:

As a strategy to improve the therapeutic success of chimeric antigen receptor T cells (CART) directed against solid tumors, we here test the combinatorial use of CART and IMSA101, a newly developed stimulator of interferon genes (STING) agonist. In two syngeneic tumor models, improved overall survival is observed when mice are treated with intratumorally administered IMSA101 in addition to intravenous CART infusion. Transcriptomic analyses of CART isolated from tumors show elevated T cell activation, as well as upregulated cytokine pathway signatures, in particular IL-18, in the combination treatment group. Also, higher levels of IL-18 in serum and tumor are detected with IMSA101 treatment. Consistent with this, the use of IL-18 receptor negative CART impair anti-tumor responses in mice receiving combination treatment. In summary, we find that IMSA101 enhances CART function which is facilitated through STING agonist-induced IL-18 secretion.

News (Medical) associated with IMSA-101

20 Sep 2022

·www.globenewswire.com

ImmuneSensor Awarded $16 Million Grant from the Cancer Prevention and Research Institute of Texas (CPRIT)

Award to support Phase 2 development of IMSA101, a STING agonist, in solid tumor malignanciesDALLAS, Sept. 20, 2022 (GLOBE NEWSWIRE) -- ImmuneSensor Therapeutics Inc. (“ImmuneSensor”), a private clinical-stage biotechnology company dedicated to harnessing innate immunity to treat cancer and autoimmune diseases, today announced the Company has been awarded a $16.1 million Product Development Research Grant from the Cancer Prevention and Research Institute of Texas (“CPRIT”) to advance Phase 2 studies evaluating IMSA101, a STING agonist, in combination with immune checkpoint inhibitors (“ICI”) and radiotherapy for the treatment of metastatic solid tumor malignancies. STING agonist in combination with immune checkpoint inhibitors (“ICI”) and other therapies such as radiotherapy can mobilize and coordinate a patient’s immune system against cancer. “We are delighted and honored to receive this grant from CPRIT which will support the continued clinical development of IMSA101. The awarding of this competitive grant following CPRIT comprehensive scientific and commercial due diligence, corroborates the encouraging preliminary data observed to date with IMSA101 as well as the therapeutic potential of the agent. This award, alongside our successful FDA meeting earlier this year, also validates the development and commercialization strategy that we have formulated for IMSA101,” said Dr. Ernest Wong, CEO of ImmuneSensor. “ImmuneSensor is a world leader in the cGAS-STING pathway, based on groundbreaking discoveries by Dr. Zhijian “James” Chen at the University of Texas Southwestern Medical Center (“UTSW”). We look forward to initiating our Phase 2 trials to further investigate the role of the cGAS-STING pathway in boosting anticancer immunity in cancer patients.” ABOUT IMSA101 IMSA101 is a small molecule agonist of the stimulator of interferon gene (“STING”) protein and is currently in development for the treatment of solid tumors. The agent has demonstrated robust tumor growth inhibition as a single agent and in combination with immune checkpoint inhibitors (“ICI”) in multiple preclinical models. The mechanism of action for IMSA101 stimulates production of crucial cytokines including interferons in a dose dependent manner and generates long-term immunity to tumors, thereby supporting its potential utility across a broad range of tumors in combination with immuno-oncology (“IO”) and non-IO therapies. IMSA101 is currently under evaluation in Phase 1 clinical studies as a monotherapy and in combination with ICI in solid tumors. Information on IMSA101 current clinical trial can be found on www.clinicaltrials.gov under the study number NCT04020185. ABOUT IMMUNESENSOR ImmuneSensor Therapeutics Inc. (“ImmuneSensor”) is a private clinical stage biotechnology company dedicated to harnessing innate immunity to treat cancer and autoimmune diseases. The company is currently developing novel medicines that target the cyclic GMP-AMP synthase (“cGAS”) – stimulator of interferon genes (“STING”) pathway to modulate the innate immune system. Based on groundbreaking discoveries from the laboratory of Dr. Zhijian “James” Chen, Professor of Molecular Biology at the University of Texas Southwestern Medical Center and a Howard Hughes Medical Institute (“HHMI”) Investigator, ImmuneSensor is developing STING activators to boost anticancer immunity and cGAS inhibitors to suppress autoimmunity when overactive. The company’s lead drug candidate, IMSA101, is currently in Phase I monotherapy and combination trial in solid tumors. The company’s pipeline also includes 2nd generation targeted STING activator drug candidates for cancer therapy, and cGAS inhibitors for the treatment of autoimmune diseases. For further information, please contact: ImmuneSensor Therapeutics Dr. Ernest Wong, CEOewong@immunesensor.com

Small molecular drug

100 Deals associated with IMSA-101

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malignant Solid Neoplasm	Phase 2	United States	ImmuneSensor Therapeutics, Inc.	07 Jul 2023
Solid tumor	Phase 2	United States	ImmuneSensor Therapeutics, Inc.	07 Jul 2023
Non-Small Cell Lung Cancer	Phase 2	United States	ImmuneSensor Therapeutics, Inc.	28 Jun 2023
Oligometastatic Disease	Phase 2	United States	ImmuneSensor Therapeutics, Inc.	28 Jun 2023
Renal Cell Carcinoma	Phase 2	United States	ImmuneSensor Therapeutics, Inc.	28 Jun 2023
Head and Neck Neoplasms	Phase 2	United States	ImmuneSensor Therapeutics, Inc.	23 Sep 2019
Hepatocellular Carcinoma	Phase 2	United States	ImmuneSensor Therapeutics, Inc.	23 Sep 2019
Hormone receptor positive breast cancer	Phase 2	United States	ImmuneSensor Therapeutics, Inc.	23 Sep 2019
Melanoma	Phase 2	United States	ImmuneSensor Therapeutics, Inc.	23 Sep 2019
Advanced cancer	Phase 1	China	PYRAMID Laboratories, Inc.	06 Sep 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05846646 (CTgov)	Phase 2	Renal Cell Carcinoma \| Oligometastatic Disease \| Non-Small Cell Lung Cancer	6	PULSAR+nivolumab+pembrolizumab	lvlnjgittg = woyncbskxa eghakyrxcw (smrdelpamm, jzfsujtowh - fxortkcisn) View more	-	20 Oct 2025
NCT04020185 (IMSA101-101, SITC2023)	Phase 1	Hepatocellular Carcinoma \| Solid tumor \| Hormone receptor positive breast cancer ... View more	-	IMSA101 monotherapy	ebtcsuqihd(fyqcrwezzb) = A single Grade 1 TEAE of cytokine release syndrome (CRS) was reported at 800 mcg. and this resolved 1 day after onset ifzbevsitz (pqussqslac ) View more	Positive	02 Nov 2023

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