VET3-TGI + Pembrolizumab for Solid Tumors

(STEALTH-001 Trial)

Recruiting at 6 trial locations

Overseen By James Burke, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: KaliVir Immunotherapeutics

Must not be taking: Anti-coagulants, Immunosuppressants

Disqualifiers: CNS metastases, Myocarditis, HIV/AIDS, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for prior systemic therapies, depending on the therapy. If you are on anti-platelet or anti-coagulant medications, you may need to stop them if they cannot be safely suspended for the trial procedures.

What data supports the effectiveness of the drug Pembrolizumab for solid tumors?

Pembrolizumab has shown effectiveness in treating various types of cancers, including non-small cell lung cancer and tumors with specific genetic features like microsatellite instability high (MSI-H) or mismatch repair deficiency (dMMR). It works by helping the immune system attack cancer cells, and has been approved for use in several cancer types due to its ability to produce durable responses. ^{1 2 3 4 5}

Is the combination of VET3-TGI and Pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA or MK-3475, has been studied in various cancers and generally shows an acceptable safety profile. Common side effects include diarrhea, fatigue, and nausea, but no major safety concerns have been identified that would prevent its use. ^{6 7 8 9 10}

What makes the drug VET3-TGI + Pembrolizumab unique for treating solid tumors?

The combination of VET3-TGI with pembrolizumab is unique because it potentially enhances the immune response against solid tumors by combining pembrolizumab, an immune checkpoint inhibitor, with VET3-TGI, which may have a novel mechanism of action not yet detailed in existing research. This combination could offer a new approach for patients with solid tumors, especially those who have limited treatment options. ^{4 7 9 11 12}

What is the purpose of this trial?

VET3-TGI is an oncolytic immunotherapy designed to treat advanced cancers. VET3-TGI has not been given to human patients yet, and the current study is designed to find a safe and effective dose of VET3-TGI when administered by direct injection into tumor(s) (called an intratumoral injection) or when given intravenously (into the vein) both alone and in combination with pembrolizumab in patients with solid tumors (STEALTH-001).

Eligibility Criteria

This trial is for adults with advanced solid tumors who have not responded to, cannot tolerate, or refused standard treatments like targeted therapy, immunotherapy, and chemotherapy. Participants must have at least one tumor that can be safely injected or biopsied and should be in good physical condition (ECOG status 0-1). They need to show proper organ function and agree to follow the study procedures.

Inclusion Criteria

My organs are functioning well.

I am willing to follow all study rules and after-treatment care instructions.

Measurable disease as per RECIST 1.1 criteria

Exclusion Criteria

I have completed the required waiting period after my last systemic therapy.

I do not have HIV/AIDS, or active hepatitis B or C.

I need blood-thinning medication that can't be stopped for certain medical procedures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation of VET3-TGI alone administered by direct injection into tumor(s) or by intravenous infusion to determine the highest tolerated dose

4 weeks

Treatment

Participants receive VET3-TGI alone or in combination with pembrolizumab at the highest tolerated dose, with booster injections or infusions permitted for up to 2 years

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

108 months

Treatment Details

Interventions

• Pembrolizumab
• VET3-TGI

Trial Overview The study tests VET3-TGI, a new oncolytic immunotherapy given directly into the tumor or through the vein. It's being tested alone and alongside pembrolizumab to find safe doses for patients with various types of solid tumors including breast, bladder, cervical cancers among others.

Participant Groups

Group I: Group D: VET3-TGI intravenous in combination with pembrolizumab Experimental Treatment 2 Interventions

VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group C. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.

Group II: Group C: VET3-TGI alone intravenous Experimental Treatment 1 Intervention

Dose escalation of VET3-TGI alone administered by IV infusion x 6. Booster infusions of VET3-TGI are permitted for up to 2 years.

Group III: Group B: VET3-TGI intratumoral in combination with pembrolizumab Experimental Treatment 2 Interventions

VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group A. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.

Group IV: Group A: VET3-TGI alone intratumoral Experimental Treatment 1 Intervention

Dose escalation of VET3-TGI alone administered by direct injection into tumor(s) x 4. Booster injections of VET3-TGI are permitted for up to 2 years.

Who Is Running the Clinical Trial?

KaliVir Immunotherapeutics

Lead Sponsor

Trials

1

Recruited

60+

Findings from Research

In a study involving 351 patients with advanced noncolorectal MSI-H/dMMR solid tumors, pembrolizumab showed a significant objective response rate (ORR) of 30.8%, indicating its efficacy in this patient population.

The treatment demonstrated a long median duration of response of 47.5 months and manageable safety, with only 11.1% of patients experiencing severe (grade 3-4) treatment-related adverse events, supporting its use in heavily pretreated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Maio, M., Ascierto, PA., Manzyuk, L., et al.[2022]

In a study of 234 patients with advanced non-small cell lung cancer (NSCLC) treated with first-line pembrolizumab, those with a poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2 had significantly lower response rates and overall survival compared to those with better performance statuses (ECOG PS 0-1).

Despite the poor outcomes, a subset of patients with ECOG PS of 2 did respond to pembrolizumab, but they were less likely to receive second-line therapies after disease progression, indicating a need for careful consideration in treatment planning for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non-small cell lung cancer and a poor performance status. Alessi, JV., Ricciuti, B., Jiménez-Aguilar, E., et al.[2021]

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

Immune checkpoint inhibitors, particularly pembrolizumab, have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), showing significant clinical activity and durable responses, especially in patients with high PD-L1 expression (TPS ⩾ 50%).

Despite the success of pembrolizumab, there is still a need for better biomarkers to identify which patients will benefit most from these treatments, as current PD-L1 testing may not fully predict patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of metastatic non-small cell lung cancer: a review of current evidence. Rihawi, K., Gelsomino, F., Sperandi, F., et al.[2023]

Pembrolizumab significantly improved progression-free survival (PFS) in patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer, with a median PFS of 16.5 months compared to 8.2 months for standard chemotherapy, indicating its efficacy as a first-line treatment.

The FDA found no safety concerns during the approval process, and while both pembrolizumab and standard of care had similar adverse reactions, the duration of treatment with pembrolizumab was nearly double that of standard care, suggesting a potentially more favorable treatment profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the First-line Treatment of Patients with MSI-H/dMMR Advanced Unresectable or Metastatic Colorectal Carcinoma. Casak, SJ., Marcus, L., Fashoyin-Aje, L., et al.[2022]

In a study of 107 patients with advanced well-differentiated neuroendocrine tumors (NETs), pembrolizumab showed limited efficacy, with an objective response rate of only 3.7%, indicating that it may not be a highly effective treatment for this specific cancer type.

Despite the low response rate, pembrolizumab was associated with manageable safety, as 75.7% of patients experienced treatment-related adverse events, with only 21.5% classified as severe (grade 3-5).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Neuroendocrine Tumors: Results From the Phase II KEYNOTE-158 Study. Strosberg, J., Mizuno, N., Doi, T., et al.[2021]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

In a study of 82 patients with metastatic NSCLC treated with Pembrolizumab, those with previous autoimmune disorders showed a trend towards improved overall survival (OS) compared to those without, with median OS of 42 months versus 10.7 months, although this was not statistically significant (p=0.073).

Patients who completed 2 years of Pembrolizumab treatment had significantly better survival outcomes (median OS not reached) compared to those who did not complete the treatment (8.7 months), highlighting the importance of treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced non-small cell lung cancer (NSCLC): Impact of autoimmune comorbidity and outcomes following treatment completion. Ansel, S., Rulach, R., Trotter, N., et al.[2023]

In a phase 3 trial involving 1174 patients with early triple-negative breast cancer, the addition of pembrolizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response to 64.8% compared to 51.2% in the placebo group, indicating enhanced treatment efficacy.

The safety profile was acceptable, with a similar incidence of severe treatment-related adverse events (grade 3 or higher) in both groups (78.0% for pembrolizumab vs. 73.0% for placebo), suggesting that pembrolizumab can be safely integrated into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Early Triple-Negative Breast Cancer. Schmid, P., Cortes, J., Pusztai, L., et al.[2022]

In a study of 21 patients with metastatic extra-pulmonary high-grade neuroendocrine neoplasms treated with pembrolizumab, only one patient showed a partial response, indicating limited efficacy of this treatment for this aggressive tumor type.

Longer progression-free survival (median 59 days) was associated with higher pre-treatment peripheral T-cell counts and lower activation of naïve T cells, suggesting that immune profile characteristics may help predict treatment outcomes and support the need for combination therapies to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impacts of pembrolizumab therapy on immune phenotype in patients with high-grade neuroendocrine neoplasms. MacFarlane, AW., Yeung, HM., Alpaugh, RK., et al.[2022]

The ongoing KEYNOTE-495/KeyImPaCT study is evaluating the effectiveness of pembrolizumab combined with other therapies in advanced non-small cell lung cancer (NSCLC), with results showing varying objective response rates (ORR) based on tumor characteristics, ranging from 0-12% in low T-cell-inflamed groups to 50-60% in high T-cell-inflamed groups.

The study confirms that assessing T-cell-inflamed gene expression profiles (TcellinfGEP) and tumor mutational burden (TMB) can help identify which patients are more likely to benefit from pembrolizumab-based treatments, while the safety profiles of the combinations remain consistent with previous findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Gutierrez, M., Lam, WS., Hellmann, MD., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non-small cell lung cancer and a poor performance status. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of metastatic non-small cell lung cancer: a review of current evidence. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the First-line Treatment of Patients with MSI-H/dMMR Advanced Unresectable or Metastatic Colorectal Carcinoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Neuroendocrine Tumors: Results From the Phase II KEYNOTE-158 Study. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced non-small cell lung cancer (NSCLC): Impact of autoimmune comorbidity and outcomes following treatment completion. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Early Triple-Negative Breast Cancer. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Impacts of pembrolizumab therapy on immune phenotype in patients with high-grade neuroendocrine neoplasms. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. [2023]