ACTM-838 for Cancer

No longer recruiting at 4 trial locations

Overseen By Shouryadeep 'Deep' Senior VP, Clinical Development, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Actym Therapeutics, Inc.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ACTM-838, a potential new drug for patients with advanced solid tumors unresponsive to standard treatments. The study is in its first phase, where researchers will determine the appropriate dose and evaluate its effectiveness. This trial may suit those with a solid tumor untreatable by existing therapies and at least one tumor measurable via scans. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that ACTM-838 is likely to be safe for humans?

Research shows that ACTM-838 has potential for treating tumors based on animal studies. In these studies, ACTM-838 remained stable and safe in animals. Tests in mice showed it was well tolerated and demonstrated better safety than a similar treatment, VNP20009, in non-human primates (NHPs).

Currently, researchers are testing ACTM-838 in early human trials, so information about its safety in humans remains limited. However, the FDA's approval of these early trials suggests some confidence in its potential safety. While more information is needed, the early signs are encouraging. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ACTM-838 because it offers a new approach to cancer treatment. Unlike traditional therapies like chemotherapy or radiation that target rapidly dividing cells, ACTM-838 is designed to specifically target and inhibit certain pathways that are crucial for cancer cell survival and proliferation. This precision could lead to fewer side effects and potentially more effective treatment outcomes. Additionally, the ability to escalate doses in a controlled manner allows for finding the optimal dose that maximizes benefits while minimizing risks.

What evidence suggests that ACTM-838 might be an effective treatment for cancer?

Research has shown that ACTM-838, the investigational treatment in this trial, has promising results in early studies. Tests on mice revealed that this treatment not only reduced tumor size but also prevented recurrence. It even helped mice avoid new tumors after treatment. The treatment strengthens the immune system, aiding the body in fighting cancer. Additionally, ACTM-838 has demonstrated compatibility with other cancer treatments, such as anti-PD1 drugs, enhancing its effectiveness. These findings suggest that ACTM-838 could be very helpful in treating advanced solid tumors. ^{1 4 6 7 8}

Who Is on the Research Team?

SVP, Clinical Development, MD, PhD

Principal Investigator

Actym Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that no longer respond to standard treatments. Participants must be in good physical condition (ECOG 0-1), have a CD4 count over 500/mL, at least one tumor visible on CT or MRI scans that can be biopsied, and their blood, liver, and heart functions should meet specific medical standards.

Inclusion Criteria

I have an advanced cancer with no standard treatment options left.

I am fully active or can carry out light work.

I have a tumor that can be measured and biopsied, visible on CT or MRI scans.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1a evaluates the safety, tolerability, and activity of escalating doses of ACTM-838 to estimate the maximum tolerated dose and/or the optimum biological dose as a monotherapy

8-12 weeks

Dose Expansion

Part 1b further evaluates ACTM-838 in patients with advanced specific tumor types at the recommended dose determined in Part 1a

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ACTM-838

Trial Overview ACTM-838 is being tested in this study. The first part of the trial will find the right dose of ACTM-838. Once the dose is determined, more people will join the second part to see how well it works at that dose against various solid tumors.

How Is the Trial Designed?

Group I: ACTM-838 Monotherapy Experimental Treatment 1 Intervention

Escalating doses of ACTM-838 in Part 1a followed by expansion in Part 1b at the recommended dose determined in Part 1a

Who Is Running the Clinical Trial?

Actym Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

Phase II trials traditionally rely on tumor shrinkage as a measure of effectiveness, but recent findings suggest that some targeted therapies may still provide survival benefits even with low response rates, highlighting the need for better evaluation methods.

The review discusses the exploration of alternative endpoints for phase II trials, such as progression-free survival and continuous tumor size measurement, which may help identify effective treatments without prematurely halting promising agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternate endpoints for screening phase II studies. Dhani, N., Tu, D., Sargent, DJ., et al.[2022]

Adoptive cell transfer (ACT) is an innovative immunotherapy that involves isolating and enhancing a patient's own immune cells to better target and fight cancer, with ongoing improvements making the process safer and more effective.

Recent developments in ACT have led to an increase in clinical trials aimed at evaluating its safety and effectiveness in treating various cancers, highlighting its growing importance in cancer treatment research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial Watch: Adoptive cell transfer for anticancer immunotherapy. Aranda, F., Vacchelli, E., Obrist, F., et al.[2021]

In a mouse model of human gastric cancer, the use of ACTIL-15 lymphocytes significantly inhibited tumor growth and improved survival rates compared to other treatments, indicating strong antitumor potential.

In a clinical trial with 63 patients suffering from advanced gastric cancer, combining ACTIL-15 lymphocytes with standard chemotherapy resulted in a median survival of 472 days, compared to 266 days for those receiving chemotherapy alone, demonstrating enhanced efficacy with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-15-induced lymphocytes as adjuvant cellular immunotherapy for gastric cancer. Hu, Y., Liu, D., Cui, P., et al.[2022]

Actein (ACT) enhances the effectiveness of TRAIL therapy in gastric cancer cells, making them more sensitive to TRAIL-induced apoptosis by altering key apoptotic proteins and increasing decoy receptors, which are dependent on the p53 pathway.

In a mouse model, the combination of ACT and TRAIL significantly inhibited gastric cancer growth compared to either treatment alone, demonstrating a promising therapeutic strategy with no observed toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Actein enhances TRAIL effects on suppressing gastric cancer progression by activating p53/Caspase-3 signaling. Yang, ZC., Ma, J.[2018]

Actinomycin D (ActD) can stabilize and activate the tumor suppressor protein p53 through two mechanisms: blocking transcription at high concentrations and inducing ribosomal stress at low concentrations, making it a candidate for p53-based cancer therapy.

The study found that the activation of p53 by ActD is mediated through the PI3K/AKT signaling pathway, as inhibitors of this pathway significantly reduced p53 expression, highlighting a specific mechanism of action that could be targeted in cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AKT mediates actinomycin D-induced p53 expression. Chen, CS., Ho, DR., Chen, FY., et al.[2021]

Daily electronic patient-reported outcomes (ePROs) significantly improved symptom management for 217 cancer patients undergoing treatment, with over 50% of assessments generating alerts for moderate to severe symptoms.

The study found that red alerts (indicating severe symptoms) were often detected without prior warnings, and these alerts were linked to a higher likelihood of acute care visits, highlighting the importance of regular monitoring in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of a Remote Monitoring Program for Symptoms Among Adults With Cancer Receiving Antineoplastic Therapy. Daly, B., Nicholas, K., Flynn, J., et al.[2022]

Actinomycin D (ActD) effectively inhibits the growth of various aerodigestive tract cancer cell lines and induces apoptosis, with IC50 values ranging from 0.021 to 2.96 nM, indicating its potential as a powerful anticancer agent.

The mechanism of action involves the activation of the p53 signaling pathway, particularly through the p53-p21 pathway, which is crucial for the apoptosis induced by low-dose ActD, supporting its use in combination therapies to enhance efficacy while potentially reducing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Context-dependent activation of p53 target genes and induction of apoptosis by actinomycin D in aerodigestive tract cancers. Adeluola, AA., Bosomtwe, N., Long, TE., et al.[2023]

Adoptive cell transfer (ACT) using OX40-driven tumor-specific CD8+ T-cells showed enhanced early differentiation and anti-apoptotic properties, which may improve their effectiveness in targeting tumors.

These OX40-driven T-cells not only proliferated effectively in tumor-bearing mice but also established long-term memory, suggesting a promising strategy for enhancing the efficacy of cancer immunotherapy with reduced toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo antitumor function of tumor antigen-specific CTLs generated in the presence of OX40 co-stimulation in vitro. Pham Minh, N., Murata, S., Kitamura, N., et al.[2018]

In a review of 36 randomized trials involving 10,484 patients with advanced gastric cancer, progression-free survival (PFS) and time to progression (TTP) were found to strongly correlate with overall survival (OS), suggesting they could serve as reliable indicators of treatment effectiveness.

The study revealed a higher correlation for PFS compared to TTP, particularly in trials conducted outside Asia and those involving patients with measurable lesions, indicating that PFS may be a more effective endpoint for evaluating new chemotherapy agents in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-free survival and time to progression as surrogate markers of overall survival in patients with advanced gastric cancer: analysis of 36 randomized trials. Shitara, K., Ikeda, J., Yokota, T., et al.[2021]

The IePRO model of care utilizes electronic patient-reported outcome (ePRO) data to actively monitor and manage symptoms in patients receiving immune checkpoint inhibitors, aiming to improve quality of care and patient outcomes.

This model is currently being evaluated in a randomized controlled trial, demonstrating a structured workflow where triage nurses respond to patient-reported symptoms, facilitating timely interventions and enhancing collaboration among care teams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of an eHealth-enhanced model of care for the monitoring and management of immune-related adverse events in patients treated with immune checkpoint inhibitors. da Silva Lopes, AM., Colomer-Lahiguera, S., Darnac, C., et al.[2023]

Cancer immunotherapy, particularly adoptive CD8+ T cell therapy (ACT), harnesses the body's immune system to target tumors, offering potential long-term protection with less toxicity compared to traditional treatments like chemotherapy and radiation.

The most successful form of ACT, anti-CD19 CAR-T cell therapy, has shown efficacy in treating B cell lymphoma and is already approved, although achieving similar success in solid tumors remains a challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive CD8+ T cell therapy against cancer:Challenges and opportunities. Jiang, X., Xu, J., Liu, M., et al.[2020]

Dual immunotherapy using aOX40 and aCTLA-4 significantly enhances CD8 T-cell responses, leading to improved survival in a mammary carcinoma model, indicating its potential as a powerful cancer treatment.

The combination therapy not only boosts the effectiveness of T-cells against tumors but also limits the production of certain cytokines that could hinder the immune response, showcasing a refined approach to cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination OX40 agonism/CTLA-4 blockade with HER2 vaccination reverses T-cell anergy and promotes survival in tumor-bearing mice. Linch, SN., Kasiewicz, MJ., McNamara, MJ., et al.[2021]

MK886, a small molecular inhibitor, shows promising antitumor activity by down-regulating actin B and disrupting the cytoskeleton in cancer cells, which may enhance the effects of treatments like UV radiation.

The low toxicity of MK886 in vivo suggests it could be safely used in humans, and its interaction with dietary lipids indicates potential for a targeted delivery system using liposomes to improve treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ingenuity network-assisted transcription profiling: Identification of a new pharmacologic mechanism for MK886. Mayburd, AL., Martlínez, A., Sackett, D., et al.[2022]

Actinomycin D (ActD) shows promise as a treatment for glioblastoma by significantly reducing tumor growth and increasing survival in mouse models, primarily by downregulating SOX2 expression.

However, ActD poses a risk of direct toxicity to primary cortical neurons, with findings indicating poor reversibility of transcription activity even after short exposures, highlighting the need for careful consideration of neurological side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival and functional recovery of primary cortical neurons exposed to actinomycin D. Lee, SE., Lee, GH.[2022]

Integrating patient-reported outcomes (PROs) into oncology practice can enhance clinical care by improving symptom monitoring and reducing the need for acute care, ultimately benefiting patient well-being.

Despite challenges such as costs and potential physician burnout, the systematic use of PROs offers significant advantages for personalized clinical decision-making and patient-centered research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translation of Patient-Reported Outcomes in Oncology Clinical Trials to Everyday Practice. Ivatury, SJ., Hazard-Jenkins, HW., Brooks, GA., et al.[2023]

Citations

1. oncotarget.com oncotarget.com/news/pr/engineered-bacterial-therapy-activates-immune-response-in-cancer-preclinical-studies/

Engineered Bacterial Therapy Activates Immune Response ... In preclinical tests, ACTM-838 shrank tumors and prevented their recurrence after treatment. Mice that were cured of tumors resisted re- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06336148

NCT06336148 | A Phase 1a/1b Study of ACTM-838 in ... Part 1b will further evaluate ACTM-838 in patients with advanced specific tumor types (defined pathologically, clinically and/or molecularly) based on data ...

3. jitc.bmj.com jitc.bmj.com/content/10/Suppl_2/A1107

1065 ACTM-838, a microbial-based ... ACTM-838 treatment showed dose- and payload-dependent anti-tumor efficacy in an anti-PD1 refractory, myeloid rich and T cell excluded, ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41048107

ACTM-838, a novel systemically delivered bacterial ... ACTM-838 showed durable anti-tumor efficacy in multiple murine tumor models and synergized with anti-PD1 therapy in combination. Keywords: IL-15; STING; ...

5. insideprecisionmedicine.com insideprecisionmedicine.com/topics/oncology/engineered-bacterial-therapy-trains-immune-system-to-fight-solid-tumors/

Engineered Bacterial Therapy Trains Immune System to ... “ACTM-838 showed durable anti-tumor efficacy in multiple murine models and synergized strongly with anti-PD1 therapy,” the authors write.

6. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/736/736410/Abstract-736-ACTM-838-safely-and-comprehensively

Abstract 736: ACTM-838 safely and comprehensively re ... In summary, we demonstrate that ACTM-838 modulates the TME and is stable and safe in animal models. Additionally, our studies recommend the ...

7. targetedonc.com targetedonc.com/view/fda-greenlights-first-in-human-trial-of-actm-838-for-advanced-solid-tumors

FDA Greenlights First-in-Human Trial of ACTM-838 ... The FDA has approved a phase 1, first-in-human trial to evaluate the safety and potential effectiveness of ACTM-838, a novel immunotherapy drug

8. cancer.gov cancer.gov/clinicaltrials/NCI-2025-00373

A Phase 1a/1b Study of ACTM-838 in Patients With ... This is a first in human (FIH) 2-part study using ACTM-838 in patients with advanced solid tumors resistant to standard of care treatment.