Safety and Efficacy Study of IMSA101 in Refractory Malignancies

NCT04020185 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: IMSA101-101
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief Summary

Open-label, dose escalation (Phase I) and dose expansion (Phase IIA) study of patients receiving intra-tumoral IMSA101 alone or in combination with an immune checkpoint inhibitor (ICI) (Phase I and II)

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-Limiting Toxicities

  Highest dose level of IMSA101 at which no more than 1 out of 6 patients experienced a dose limiting toxicity (DLT) during the first cycle (28 days) of therapy.

  Cycle 1 (28 days) of therapy

Secondary Outcomes (1)

• Best Overall Response

  9 months

Study Arms (5)

Ph I Monotherapy

EXPERIMENTAL

* Dose escalation design in which administered dose levels of IMSA101 as monotherapy will be escalated stepwise in successive cohorts of 3 to 6 patients per dose group (using a standard 3+3 study design) of IMSA101 until the RP2D or maximum tolerated dose (MTD) level is identified. * The first patient enrolled in each dose level must complete the first two weeks of Cycle 1 prior to enrolling the second and third patients. * Dose levels to be evaluated include (although not necessarily limited to) 100 µg (representing 1/60th of the pre-clinical Highest Non-Severely Toxic Dose \[HNSTD\] dose), 200 µg, 400 µg, 800 µg, and 1,200 µg.

Drug: IMSA101

Ph I Combination Therapy

EXPERIMENTAL

* Ph I combination dosing of IMSA101 shall be evaluated upon satisfaction of the following criteria: * A given dose level (combo dose level 1) has been confirmed as safe for monotherapy dosing (i.e. 2/6 patients experience Cycle 1 DLT). * The next higher dose level (combo dose level 2) has been confirmed as safe for monotherapy dosing (i.e. 2/6 patients experience Cycle 1 DLT). * The dose level (combo dose level 1) is found to demonstrate adequate IMSA101 pharmacodynamic (PD) activity based on exploratory endpoints. * Eligible patients shall have demonstrated RECIST stable disease through ≥ 4 consecutive cycles of an approved PD-1/PD-L1-targeted ICI with no Grade ≥ 3 CTCAE events considered to be drug-related. * Safety evaluations and dose escalation of IMSA101 administered in combination with current therapy shall proceed in a manner consistent with monotherapy escalation and shall proceed independently of monotherapy dose escalation.

Drug: IMSA101; Drug: Immune checkpoint inhibitor (ICI)

Ph II Monotherapy (Arm A)

EXPERIMENTAL

* This dose-expansion arm of 20 patients is intended to confirm the tolerability of the RP2D and identify provocative signals of IMSA101 anti-tumor activity when administered as monotherapy * Tumor type to be evaluated will be identified prior to Phase IIA commencement and will be documented in a protocol amendment.

Drug: IMSA101

Ph II Combination Therapy (Arm B)

EXPERIMENTAL

* This dose-expansion arm of 20 patients is intended to confirm the tolerability of the RP2D and identify provocative signals of IMSA101 anti-tumor activity when administered as combination therapy with PD-1/PD-L1 targeted immune checkpoint inhibitors. * This arm shall include a safety run-in of 5-10 patients. * Tumor type and corresponding treatment combination will be identified prior to Phase IIA commencement and documented in a protocol amendment.

Drug: IMSA101; Drug: Immune checkpoint inhibitor (ICI)

Ph II Combination Therapy (Arm C)

EXPERIMENTAL

* This dose-expansion arm of 20 patients is intended to confirm the tolerability of the RP2D and identify provocative signals of IMSA101 anti-tumor activity when administered as combination therapy with non-PD-1/PD-L1-targeted immuno-oncology (IO) drugs approved by the FDA. * This arm shall include a safety run-in of 5-10 patients. * Tumor type and corresponding treatment combination will be identified prior to Phase IIA commencement and documented in a protocol amendment..

Drug: IMSA101; Drug: Immuno-oncology (IO) therapy

Interventions

IMSA101 DRUG

IMSA101 administered by intra-tumoral (IT) injection on Day 1 of Weeks 1, 2, and 3 for Cycle 1 and on Day 1 of Weeks 1 and 3 for all subsequent cycles.

Ph I Combination Therapy; Ph I Monotherapy; Ph II Combination Therapy (Arm B); Ph II Combination Therapy (Arm C); Ph II Monotherapy (Arm A)

Immune checkpoint inhibitor (ICI) DRUG

Administered according to product label

Ph I Combination Therapy; Ph II Combination Therapy (Arm B)

Immuno-oncology (IO) therapy DRUG

Administered according to product label

Ph II Combination Therapy (Arm C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent and mental capability to understand the informed consent
• Male or female patients \> 18 years of age
• Histologically or cytologically documented locally advanced or metastatic solid tumor malignancies refractory to or otherwise ineligible for treatment with standard-of-care agents/regimens, including but not limited to:
• Malignant melanoma
• Hormone receptor negative breast cancer
• Gastro-esophageal cancer
• Non-small cell lung cancer
• Head and neck cancer
• Hepatoma
• Renal cell carcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Evaluable or measurable disease as follows:
• A minimum of 3 RECIST-evaluable lesions: one that is suitable for injection and biopsied; one non-injected that will be biopsied for abscopal effect; and one measurable lesion that will be followed for response only.
• Injectable tumors shall be accessed by intralesional (cutaneous) or percutaneous injection only, including those lesions that are visible, palpable, or detectable by standard radiographic or ultrasound methods. Neither surgical procedures nor endoscopically-guided injections including those to endobronchial, endoluminal, or endosinusial spaces shall be allowed. While no anatomic locations are required or disallowed, lesions selected for intratumoral injection must, in the opinion of the investigator:
• Not be immediately adjacent to blood vasculature or other physiologic landmarks in such a way that will accrue undue safety risk to the patient

You may not qualify if:

• Anti-cancer therapy within 4 weeks or \< 5 half-lives of the first dose of study drug.
• Failure to recover to Grade 1 or less from clinically significant AEs due to prior anti-cancer therapy.
• Known untreated brain metastases or treated brain metastases that have not been stable (scan showing no worsening of central nervous system (CNS) lesion\[s\] and no requirement of corticosteroids) ≥ 4 weeks prior to study enrollment
• Baseline prolongation of QT/QTc interval (QTc interval \> 470)
• Uncontrolled intercurrent illness (including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations) that in opinion of the investigator would limit compliance with study requirements
• Women who are pregnant or breastfeeding
• Phase I combination only: Prior tumor progression through PD-1 or PD-L1 targeted ICI therapy.

Sponsors & Collaborators

• ImmuneSensor Therapeutics Inc.: lead

Study Sites (6)

Honor Health

Scottsdale, Arizona, 85260, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Atlantic Health System/Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Jacoby J, Mahalingam D, Alistar A, Garmey E, Kazmi S, Mooneyham T, Sun L, Yap TA, Vu P, Moser J. Phase 1 first-in-human dose-escalation study of IMSA101, a novel cyclic di-nucleotide STING agonist, for patients with advanced solid tumor malignancies. J Immunother Cancer. 2025 Jun 18;13(6):e011572. doi: 10.1136/jitc-2025-011572.

  PMID: 40533265 DERIVED

MeSH Terms

Interventions

Immune Checkpoint Inhibitors; Jupiter; Therapeutics

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Planets; Solar System; Astronomical Objects; Astronomical Phenomena; Physical Phenomena

Results Point of Contact

• Title: Vice President of Clinical Operations and Project Management
• Organization: ImmuneSensor Therapeutics Inc.

tmooneyham@immunesensor.com

210-380-5164

Study Officials

• Teresa S Mooneyham

  Vice President, ImmuneSensor Therapeutics Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase I includes a monotherapy arm and an immune checkpoint inhibitor (ICI) combination therapy arm Phase II includes three arms, Arm A monotherapy, Arm B immuno-oncology (IO) combination therapy, Arm C IO combination therapy

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 15, 2019
• Study Start: September 23, 2019
• Primary Completion: September 15, 2023
• Study Completion: September 15, 2023
• Last Updated: December 11, 2024
• Results First Posted: December 11, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)