XTX301 for Solid Tumors

Recruiting at 12 trial locations

Overseen By Xilio Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Xilio Development, Inc.

Must not be taking: Immunosuppressants, IL-12 therapy

Disqualifiers: Liver metastasis, CNS malignancy, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

358 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new treatment called XTX301 (tumor-activated IL-12) for individuals with advanced solid tumors. It aims to determine the safety and efficacy of XTX301 against various cancers, including head and neck cancer, melanoma, lung cancer, ovarian cancer, prostate cancer, and triple-negative breast cancer. The trial targets those who have exhausted other treatment options. Participants must have specific types of cancer that have spread or recurred and have previously undergone certain therapies. Individuals with a solid tumor meeting these criteria and who have not received IL-12 therapy may qualify. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop my current medications for the XTX301 trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that ongoing medical castration must be maintained for prostate cancer patients, suggesting some treatments may continue. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that XTX301 is likely to be safe for humans?

Research shows that XTX301 targets tumors specifically while minimizing impact on healthy tissues, which should reduce the risk of side effects. Although XTX301 is being tested in humans for the first time, earlier studies suggest it could be safer at effective doses.

Since this study is in its early stages, the main goal is to determine if XTX301 is safe and well-tolerated. Researchers are carefully monitoring for any side effects and determining the right dose. New treatments in these phases undergo close monitoring to ensure participant safety. While detailed human data remains limited, these steps help ensure that any risks are understood and managed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for solid tumors, which often include surgery, chemotherapy, and radiation, XTX301 is unique because it works by targeting specific tumor types at a molecular level. This treatment is designed to be more precise, potentially reducing side effects and improving outcomes compared to traditional options. Researchers are excited about XTX301 because it aims to provide a more targeted approach for various cancers, such as head and neck squamous cell carcinoma, melanoma, non-small cell lung cancer, ovarian cancer, castrate-resistant prostate cancer, and triple-negative breast cancer. By honing in on specific tumor characteristics, XTX301 has the potential to offer a new, effective option for patients who may not respond well to existing therapies.

What evidence suggests that XTX301 might be an effective treatment for solid tumors?

Research shows that XTX301 could be a promising treatment for various advanced solid tumors. In early lab studies, XTX301, a special form of interleukin-12 that boosts the immune system, showed potential for treating solid tumors more effectively. These studies suggest that XTX301 might work better and more safely than traditional methods because it can be used in a wider range of doses without causing harm. This potential has been observed in several types of cancer, including melanoma, lung, and ovarian cancers. The current trial tests XTX301 in different phases to evaluate its safety and antitumor activity in specific cancer cohorts, such as head and neck squamous cell carcinoma, melanoma, non-small cell lung cancer, ovarian cancer, castrate-resistant prostate cancer, and triple-negative breast cancer. However, limited information exists on its effectiveness in humans, as XTX301 is currently being tested for safety and behavior in the body. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors like melanoma, lung, breast, and prostate cancer that have not responded to standard treatments. Participants must be in a stable condition (ECOG 0-2), have good organ function, and be able to provide tumor tissue samples. People with liver metastasis, active brain cancers or infections like hepatitis B/C, recent transplants or severe immune-related reactions from past immunotherapies cannot join.

Inclusion Criteria

I can take care of myself and perform daily activities.

My organs are working well.

My cancer is advanced or has spread, and standard treatments haven't worked or aren't suitable.

Exclusion Criteria

I have an active hepatitis B or C infection.

I have previously been treated with IL-12 therapy.

I do not have an active brain tumor or cancer spread to my brain or its coverings.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment - Dose Escalation

XTX301 monotherapy administered in ascending doses to assess safety, tolerability, and determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D)

8-12 weeks

Phase 1 Treatment - Pharmacodynamics Expansion

Evaluation of XTX301 in patients with selected advanced solid tumors to further characterize the pharmacodynamics profile

8-12 weeks

Phase 2 Treatment - Disease-Specific Cohorts

Further evaluation of safety and antitumor activity/efficacy of XTX301 in disease-specific expansion cohorts

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• XTX301

Trial Overview XTX301 is being tested as a solo treatment for various advanced solid tumors. This first-in-human study aims to see how safe it is and what effects it has on patients who've run out of standard treatment options. It involves taking biopsies before and after starting the drug to closely monitor its impact.

How Is the Trial Designed?

Group I: Phase 2 - XTX301 Monotherapy Dose Expansion in Disease-Specific Cohorts Experimental Treatment 1 Intervention

Phase 2 will further evaluate the safety and antitumor activity/efficacy of XTX301 monotherapy in disease-specific expansion cohorts of patients with select tumors, namely: * Cohort 2A: head and neck squamous cell carcinoma (HNSCC) * Cohort 2B: melanoma (patients with uveal melanoma are excluded) * Cohort 2C: non-small cell lung cancer (NSCLC) * Cohort 2D: ovarian cancer * Cohort 2E: castrate-resistant prostate cancer (CRPC) * Cohort 2F: triple-negative breast cancer (TNBC)

Group II: Phase 1 - XTX301 Monotherapy Dose Escalation and Pharmacodynamics Expansion Experimental Treatment 1 Intervention

Part 1A Dose Escalation of XTX301 administered in ascending doses to patients with advanced solid tumors to assess the safety and tolerability and determine/define MTD and/or the highest recommended Phase 2 dose (RP2D). Part 1B Evaluation of XTX301 in patients with selected advanced solid tumors to further characterize the pharmacodynamics profile of XTX301.

Who Is Running the Clinical Trial?

Xilio Development, Inc.

Lead Sponsor

Trials

3

Recruited

680+

Published Research Related to This Trial

XTX301 is a novel tumor-activated form of IL12 that shows significant antitumor activity in mouse models without causing systemic toxicity, suggesting a safer alternative to traditional IL12 administration.

In a nonhuman primate study, XTX301 was well-tolerated at doses higher than those effective in mice, indicating its potential for effective cancer treatment with a wider safety margin, and it is currently being tested in a phase I clinical trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

XTX301, a tumor-activated Interleukin-12 has the potential to widen the therapeutic index of IL-12 treatment for solid tumors as evidenced by pre-clinical studies. Patel, E., Malkova, NV., Crowe, D., et al.[2023]

In a phase 1 trial involving 31 patients with recurrent high-grade glioma, the hIL-12 gene therapy showed acceptable safety and tolerability, with dose-related increases in hIL-12 and interferon-γ observed, indicating a potential immunological antitumor effect.

Patients receiving a 20 mg dose of the oral activator veledimex (VDX) had a median overall survival of 12.7 months, while concurrent high doses of corticosteroids negatively impacted survival outcomes, highlighting the importance of managing steroid use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial. Chiocca, EA., Yu, JS., Lukas, RV., et al.[2023]

A high-capacity adenoviral vector delivering interleukin-12 (IL-12) significantly reduced tumor burden and improved overall survival in a model of pediatric osteosarcoma, demonstrating its potential as a therapeutic intervention.

The treatment not only eradicated tumors but also induced long-term immunological memory in survivors, suggesting that it could provide lasting protection against tumor recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local administration of IL-12 with an HC vector results in local and metastatic tumor control in pediatric osteosarcoma. Zalacain, M., Bunuales, M., Marrodan, L., et al.[2021]

Lentiviral transduction of human sarcoma cells to produce interleukin-12 (IL-12) allows for localized delivery of this cytokine, enhancing both innate and adaptive immune responses without the systemic toxicities associated with traditional IL-12 administration.

In murine models, IL-12 expressing sarcomas not only restricted tumor growth but also triggered a specific immune response, indicating that this method could be a promising approach for treating sarcomas through autologous reintroduction of modified tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sarcoma IL-12 overexpression facilitates NK cell immunomodulation. Rademacher, MJ., Cruz, A., Faber, M., et al.[2021]

A novel therapeutic system using membrane-anchored IL-12 (aIL-12) delivered by tumor-specific T cells showed increased antitumor efficacy while maintaining low systemic exposure to IL-12, minimizing potential toxicity.

In both murine and human tumor models, the NFAT-inducible aIL-12 construct improved antitumor responses without causing detectable levels of IL-12 in serum or weight loss, indicating a safer and more effective approach to cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced efficacy and limited systemic cytokine exposure with membrane-anchored interleukin-12 T-cell therapy in murine tumor models. Zhang, L., Davies, JS., Serna, C., et al.[2020]

Interleukin-12 (IL-12) has shown strong potential to boost antitumor immune responses, but its initial clinical use faced challenges due to a poor benefit-toxicity ratio.

Localized delivery methods for IL-12, such as electroporation of plasmid DNA and combination with checkpoint inhibitors, have improved its therapeutic effectiveness and safety, showing promising results in early-phase clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel strategies exploiting interleukin-12 in cancer immunotherapy. Cirella, A., Luri-Rey, C., Di Trani, CA., et al.[2022]

Human lung tumor biopsies can be successfully implanted into SCID mice, maintaining their viability and tumor microenvironment characteristics for at least 3 months, allowing for the study of tumor dynamics in a controlled setting.

Inflammatory cells within these tumor xenografts can suppress tumor growth through the production of interleukin-12 (IL-12), and this effect can be enhanced by delivering IL-12 using biodegradable microspheres, highlighting the potential for targeted cytokine therapies in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human inflammatory cells within the tumor microenvironment of lung tumor xenografts mediate tumor growth suppression in situ that depends on and is augmented by interleukin-12. Sugiyama, Y., Kato, M., Chen, FA., et al.[2019]

The IL-12 family cytokines, including IL-12, IL-23, IL-27, IL-35, and IL-39, play crucial roles in regulating immune responses in cancer, with IL-12 acting as an effector cytokine that enhances anti-tumor immunity by activating cytotoxic T and NK cells.

While IL-12 promotes anti-tumor effects, other family members like IL-23 and IL-27 can have dual roles, potentially aiding tumor growth, and IL-35 primarily inhibits effector T cells, suggesting that these cytokines could be targeted for immunomodulatory therapies in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-12 Family Cytokines in Cancer and Immunotherapy. Mirlekar, B., Pylayeva-Gupta, Y.[2021]

mWTX-330, a novel INDUKINE molecule, shows promising antitumor activity in mice by selectively activating immune cells within tumors while minimizing systemic toxicity, making it a safer option for cancer immunotherapy.

The effectiveness of mWTX-330 relies on its ability to be processed by tumor-specific proteases, enhancing the immune response through mechanisms like increasing polyfunctional CD8+ T cells and reducing exhausted T cells, which are crucial for effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mWTX-330, an IL-12 INDUKINE Molecule, Activates and Reshapes Tumor-Infiltrating CD8+ T and NK Cells to Generate Antitumor Immunity. Nirschl, CJ., Brodkin, HR., Domonkos, C., et al.[2023]

Interleukin-12 (IL-12) has shown strong antitumor effects in preclinical models, but its systemic delivery in early clinical trials led to significant toxicities, limiting its use in humans.

Recent advancements in localized delivery systems for IL-12, such as immunocytokine fusions and polymeric nanoparticles, have demonstrated promising antitumor immunity with fewer side effects, suggesting a potential resurgence in IL-12-based cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localized Interleukin-12 for Cancer Immunotherapy. Nguyen, KG., Vrabel, MR., Mantooth, SM., et al.[2021]

The novel immunocytokine NHS-IL12, which combines IL-12 with a tumor-targeting antibody, shows a longer plasma half-life and selective targeting to tumors, making it a potentially safer and more effective cancer treatment compared to standard recombinant IL-12.

NHS-IL12 demonstrated superior anti-tumor effects in murine models, primarily through CD8+ T cell activation, and when combined with other therapies like vaccines or chemotherapy, it produced even greater anti-tumor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The immunocytokine NHS-IL12 as a potential cancer therapeutic. Fallon, J., Tighe, R., Kradjian, G., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05684965

XTX301 in Patients With Advanced Solid Tumors This is a first-in-human, multicenter, Phase 1/2, open-label study designed to evaluate the safety, tolerability, PK, PD, immunogenicity, and antitumor ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10993987/

XTX301, a Tumor-Activated Interleukin-12 Has the ... A tumor-activated interleukin-12 has the potential to widen the therapeutic index of IL12 treatment for solid tumors as evidenced by preclinical studies.

3. ir.xiliotx.com ir.xiliotx.com/static-files/f8f58578-794a-499b-9c35-ba24127d861d

Spotlight on XTX301, a Novel Tumor- Activated, Engineered IL ... Plan to initially evaluate XTX301 as a monotherapy for the treatment of advanced solid tumors. Page 8. 8. Unmet Need in. Cancer. "Cold ...

4. yalemedicine.org yalemedicine.org/clinical-trials/xtx301-xtx301-in-patients-with-advanced-solid-tumors

XTX301 in Patients With Advanced Solid Tumors This is a first-in-human, multicenter, Phase 1, open-label study designed to evaluate the safety and tolerability of XTX301 as monotherapy in ...

5. aacrjournals.org aacrjournals.org/mct/article-pdf/doi/10.1158/1535-7163.MCT-23-0336/3387877/mct-23-0336.pdf

1 XTX301, a tumor-activated Interleukin-12 has the potential to ... melanoma, colorectal, head and neck (H&N), prostate, lung, ovarian, or renal cell carcinoma (RCC). 134 patients were obtained from the Cooperative Human ...

6. xiliotx.com xiliotx.com/wp-content/uploads/2023/06/2023_ASCO_Annual_Meeting_Poster_Final.pdf

A First-in-Human Study of XTX301, a Masked, Tumor- ... XTX301 is designed to produce a localized anti-tumor immune response while limiting exposure of the active form of XTX301 in non-tumor tissue, and thereby.

7. delta.larvol.com delta.larvol.com/Products/?ProductId=09c0076d-dc9e-49a9-a1f9-bc055ceb1212

XTX301 / Xilio Therap, Gilead ... Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast ...