FDA Greenlights First-in-Human Trial of ACTM-838 for Advanced Solid Tumors (2024)

• The FDA has approved a phase 1 trial of ACTM-838 (NCT06336148) for the treatment of solid tumors.

• The first-in-human trial will assess safety, tolerability, payload delivery, and early signs of effectiveness in patients with advanced solid tumors who have exhausted standard treatments.

• Part 1a aims to determine the maximum tolerated or optimal dose, and part 1b will evaluate the agent in specific tumor types at the recommended dose.

The FDA has approved an investigational new drug (IND) application that initiates a phase 1 trial of ACTM-838 for the treatment of solid tumors.1

ACTM-838 delivers immunomodulatory payloads, engineered IL-15 plex, and STING, to tumor-resident phagocytic antigen-presenting cells within the tumor microenvironment (TME).

The first-in-human trial of ACTM-838 plans to assess its safety, tolerability, payload delivery, and preliminary efficacy when given at escalating doses and used as a single agent. The open-label, monotherapy, dose-escalation study plans to enroll patients with advanced solid tumors that are resistant to standard-of-care treatments.

“The immunosuppressive TME is a key challenge in the treatment of solid tumors, limiting the efficacy of many potentially effective anticancer drugs. Actym Therapeutics has developed an innovative technology to specifically deliver and express constitutively active STING in tumor-resident myeloid cells using a systemically administered therapy. IL-15plex expression adds complementary activity on B, T, and [natural killer] cells, achieving durable antitumor immunity,” said Jason J. Luke, MD, FACP, a leading international physician-scientist specializing in the clinical development of immunotherapies for solid tumors, in a press release.

“Actym’s approach to modulating the TME has a unique potential to overcome these immunological barriers. Their lead candidate, ACTM-838, was shown to be safe and effective in preclinical studies and is now ready to enter the clinic,” continued Luke.

This study includes 2 parts.² In part 1a, investigators will examine the safety, tolerability, and activity of ACTM-838 to estimate the maximum tolerated dose and/or the optimum biological dose when given alone. This will be utilized to determine the recommended dose for part 1b, which will further evaluate the agent in patients with advanced specific tumor types.

Patients are eligible for enrollment in the study if they have an advanced solid tumor that does not respond to standard curative therapy, if there is no therapy that has demonstrated survival benefit, or if they are ineligible to receive or refuse to receive such therapy. Other requirements include having at least 1 measurable lesion per RECIST v1.1; amenable for biopsy, and radiographically apparent on CT or MRI, an ECOG performance status of 0 or 1, adequate hematologic, hepatic, and cardiac function, and CD4 count >500/mL at screening.

The primary end points of the study include evaluating the incidence and severity of adverse events (AEs) and serious AEs, dose-limiting toxicities, objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), change in tumor markers, and amount of ACTM-838 in the blood, urine, and feces, as measured by digital droplet-polymerase chain reaction.

With an estimated enrollment of 35 patients, the study will be conducted at clinical sites in the United States and Australia.¹

“The IND clearance for ACTM-838 is a major milestone for Actym and potentially a significant step forward in harnessing the power of immunotherapy to treat patients with solid tumors more effectively,” added Tom Smart, chief executive officer of Actym, in a press release. “It is terrific to see the vision and impressive work pioneered by Actym’s founders translated into a promising clinical-stage asset. As we advance our lead clinical program, we also look forward to further expanding the potential applications of our STACT™ biological platform by developing new product candidates in-house and in collaboration with pharmaceutical companies.”

REFERENCES

1. Actym Therapeutics announces IND clearance for phase 1 clinical trial investigating lead program ACTM-838 in patients with solid tumors. News release. May 30, 2024. Accessed May 30, 2024. https://tinyurl.com/nhkke53u

2. A phase 1a/1b study of ACTM-838 in patients with advanced solid tumors. ClinicalTrials.gov. Updated March 28, 2024. Accessed May 30, 2024. https://clinicaltrials.gov/study/NCT06336148?term=ACTM-838&rank=1&tab=table