MDX2001 for Advanced Solid Tumors

Recruiting at 4 trial locations

Overseen By Email recommended

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ModeX Therapeutics, An OPKO Health Company

Disqualifiers: Cardiac disease, Brain metastases, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 6 months

115 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is designed to characterize the safety, tolerability, and anti-tumor activity of MDX2001 in patients with advanced solid tumors.

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 team or your doctor.

What data supports the effectiveness of the drug MDX2001 for advanced solid tumors?

The research does not provide direct evidence about the effectiveness of MDX2001 for advanced solid tumors, but similar studies on other treatments for advanced solid tumors, like VX15/2503 and MEDI-573, have shown some antitumor activity, suggesting potential for MDX2001. ^{1 2 3 4 5}

What safety data exists for MDX2001 in humans?

The safety data for treatments similar to MDX2001, such as PD-L1 inhibitors, show that they generally have fewer treatment-related side effects compared to traditional chemotherapy, although they may cause immune-related side effects. These side effects are usually mild to moderate, but some patients may experience severe reactions. ^{6 7 8 9 10}

Eligibility Criteria

Adults over 18 with advanced solid tumors like lung, breast, prostate, and various other cancers. They must have a performance status indicating they can care for themselves (ECOG 0-1) and at least one measurable tumor. Participants need proper organ function and must follow local contraception guidelines.

Inclusion Criteria

I have at least one tumor that can be measured by medical imaging.

My cancer has spread and was confirmed by lab tests.

My blood, liver, and kidney functions are all within normal ranges.

Exclusion Criteria

I have no lingering side effects from past cancer treatments.

Known hypersensitivity to MDX2001 or any of its ingredients

I have had a transplant of an organ or bone marrow.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive MDX2001 as intravenous (IV) infusion during dose escalation and expansion phases

up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 months

Long-term follow-up

Participants may continue to be monitored for long-term safety and efficacy

up to 9 months

Treatment Details

Interventions

• MDX2001

Trial Overview The trial is testing MDX2001's safety, tolerability, and effectiveness against advanced solid tumors. It involves gradually increasing the dose of MDX2001 to find the highest dose patients can take without serious side effects before expanding to more participants.

Participant Groups

Group I: Phase 2a - Cohort Expansion Experimental Treatment 1 Intervention

Patients with a single tumor indication will receive MDX2001 as intravenous (IV) infusion at the recommended Phase 2 dose.

Group II: Phase 1b - Dose Expansion - Dose B Experimental Treatment 1 Intervention

Patients with a single tumor indication will receive MDX2001 as intravenous (IV) infusion.

Group III: Phase 1b - Dose Expansion - Dose A Experimental Treatment 1 Intervention

Patients with a single tumor indication receive MDX2001 as intravenous (IV) infusion.

Group IV: Phase 1a - MDX2001 Dose Escalation Experimental Treatment 1 Intervention

Patients with metastatic solid tumors will receive MDX2001 as intravenous (IV) infusion.

Who Is Running the Clinical Trial?

ModeX Therapeutics, An OPKO Health Company

Lead Sponsor

Trials

2

Recruited

170+

Findings from Research

VX15/2503 was well tolerated in a study of 42 patients with advanced solid tumors, with most side effects being mild (grade 1 or 2), such as nausea and fatigue, indicating a favorable safety profile.

The treatment showed promising antitumor activity, with one patient achieving a partial response and 45.2% of patients maintaining stable disease for at least 8 weeks, suggesting that VX15/2503 may enhance immune response against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Solid Tumors. Patnaik, A., Weiss, GJ., Leonard, JE., et al.[2022]

The maximum tolerated dose (MTD) of OSI-461 was determined to be 1,000 mg taken orally twice daily in combination with mitoxantrone, with the combination generally well tolerated by patients with advanced solid tumors.

Out of the patients studied, 10% experienced a partial response and 50% had stable disease, indicating that while the combination was safe, the response rates were similar to those seen with mitoxantrone alone, leading to the decision not to pursue further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone. Resta, LP., Pili, R., Eisenberger, MA., et al.[2021]

In low-risk myelodysplastic syndromes (MDS), treatments like growth factor support, lenalidomide, and luspatercept aim to reduce transfusion needs and improve quality of life, while high-risk MDS treatments focus on improving survival with hypomethylating agents and stem cell transplantation.

Recent advancements in treatment combinations, including new hypomethylating agents and the approval of an oral hypomethylating agent, show promise for improving outcomes in high-risk MDS patients, although there remains a significant need for effective therapies for relapsed and refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Therapy of the Patients with MDS: Walking towards Personalized Therapy. Palacios-Berraquero, ML., Alfonso-Piérola, A.[2021]

Chemotherapy has been shown to improve survival and quality of life in patients with advanced non-small cell lung cancer, including those with poor performance status (PS2), who historically have been underrepresented in clinical trials.

Recent studies indicate that PS2 patients can benefit from chemotherapy, with combination treatments like carboplatin and paclitaxel potentially offering better outcomes than single-agent therapies, without significantly increased toxicity compared to fitter patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of chemotherapy in patients with poor performance status and advanced non-small cell lung cancer. Langer, C., Lilenbaum, R.[2019]

In a phase I study involving 43 patients with advanced solid tumors, MEDI-573 demonstrated a favorable safety profile with no dose-limiting toxicities and only one case of treatment-related hyperglycemia.

While MEDI-573 did not lead to any partial or complete responses in the tumors, 13 out of 39 evaluable patients showed stable disease, indicating some preliminary antitumor activity in a heavily pretreated population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Haluska, P., Menefee, M., Plimack, ER., et al.[2021]

In a network meta-analysis of six phase III clinical trials involving 4053 patients, PD-L1 inhibitor monotherapy was found to significantly reduce the risk of treatment-related adverse events (AEs) compared to platinum-based chemotherapy, with a risk ratio of 0.722 for any grade AEs and 0.406 for grade 3-5 AEs.

While PD-L1 inhibitors showed improved safety outcomes overall, they were associated with a higher risk of immune-related AEs compared to chemotherapy, indicating a need for careful monitoring in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis. García Campelo, MR., Arriola, E., Campos Balea, B., et al.[2021]

The virtual multidisciplinary immune-related toxicity (IR-tox) team was successfully implemented, receiving 117 referrals from 102 patients in just 8 months, with all recommendations provided within 24 hours.

100% of referring providers utilized the IR-tox team's recommendations, and 74% reported changing patient management based on these recommendations, highlighting the team's effectiveness in addressing immune-related adverse events from immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multidisciplinary Toxicity Team for Cancer Immunotherapy-Related Adverse Events. Naidoo, J., Zhang, J., Lipson, EJ., et al.[2020]

A comprehensive review of 41 randomized controlled trials involving 23,121 patients found that treatments combining chemotherapy with immune checkpoint inhibitors (ICIs) significantly increased the risk of treatment-related adverse events compared to ICI-only regimens.

Among the various ICI treatments, the combination of PD-L1 and CTLA-4 with chemotherapy had the highest risk of immune-related adverse events, with severe cases like myocarditis and pneumonitis showing notably high fatality rates, indicating the need for careful monitoring and management in patients receiving these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system. Yan, YD., Zhao, Y., Zhang, C., et al.[2022]

Anti-PD-1/PD-L1 antibody therapy significantly improved overall survival and progression-free survival in advanced non-small cell lung cancer (NSCLC) patients compared to docetaxel, with hazard ratios indicating a 31% and 24% reduction in risk of death and disease progression, respectively.

This therapy also demonstrated a higher objective response rate and fewer treatment-related adverse events, particularly severe ones, suggesting it is a safer and more effective option for patients previously treated for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of anti-PD-1/PD-L1 antibody therapy versus docetaxel for pretreated advanced NSCLC: a meta-analysis. Huang, G., Sun, X., Liu, D., et al.[2019]

Ipilimumab has shown a positive impact on overall survival in patients with stage IV melanoma, with long-term follow-up indicating its effectiveness compared to conventional treatments.

While 84.8% of patients experience drug-related adverse events, most are mild to moderate; however, severe reactions can occur, necessitating careful monitoring and management, especially when combined with other therapies like vemurafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. Camacho, LH.[2022]

References

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

Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Solid Tumors. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Current Therapy of the Patients with MDS: Walking towards Personalized Therapy. [2021]

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

Role of chemotherapy in patients with poor performance status and advanced non-small cell lung cancer. [2019]

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

Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis. [2021]

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

A Multidisciplinary Toxicity Team for Cancer Immunotherapy-Related Adverse Events. [2020]

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

Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system. [2022]

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

The efficacy and safety of anti-PD-1/PD-L1 antibody therapy versus docetaxel for pretreated advanced NSCLC: a meta-analysis. [2019]

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

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. [2022]