MGC018 + MGD019 for Solid Tumors

Recruiting at 10 trial locations

Overseen By Global Trial Manager

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MacroGenics

Must not be taking: B7-H3 agents

Disqualifiers: Other malignancy, Active infection, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 21

Duration: Up to 2 years

278 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests two experimental drugs on patients with advanced cancers that haven't responded to other treatments. One drug aims to kill cancer cells directly, while the other boosts the immune system to fight the cancer.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug MGC018 + MGD019 for solid tumors?

Research shows that combining drugs targeting PD-1 and CTLA-4, like MGD019, can improve cancer treatment outcomes compared to using single drugs. MGD019, a bispecific antibody, has shown promising results in early trials, with some patients experiencing positive responses in tumors that usually don't respond to similar treatments. ^{1 2 3 4 5}

Is the treatment MGC018 + MGD019 generally safe for humans?

The treatment MGD019, which is part of the combination, has been found to be generally safe in early human studies for patients with advanced solid tumors, showing acceptable safety levels. It was also well tolerated in non-human primates, indicating a promising safety profile. ^{1 2 3 6 7}

What makes the drug MGC018 + MGD019 unique for treating solid tumors?

This drug is unique because it combines two immune checkpoint inhibitors, PD-1 and CTLA-4, into a single bispecific molecule, MGD019, which enhances the immune response against tumors by blocking both pathways simultaneously. This approach aims to improve effectiveness in tumors that typically do not respond well to single-agent checkpoint inhibitors. ^{1 2 3 8 9}

Research Team

Denise Casey, M.D.

Principal Investigator

MacroGenics

Eligibility Criteria

This trial is for adults with advanced solid tumors, including specific cancers like prostate, melanoma, pancreatic, liver, ovarian, and kidney cancer. Participants must have a life expectancy of at least 12 weeks and should have tried approved treatments already. They need to be able to consent to the study's procedures and agree to use effective contraception. People with certain medical conditions or those who've had other recent malignancies are not eligible.

Inclusion Criteria

I have an advanced solid tumor, such as prostate, melanoma, pancreatic, liver, ovarian, or kidney cancer.

Your organs are working well, as shown in your lab test results.

I have an advanced solid tumor such as prostate, melanoma, pancreatic, liver, ovarian, or kidney cancer.

Exclusion Criteria

I have a history of Guillain-Barre syndrome, myasthenia gravis, or similar conditions.

I have had a stem cell or organ transplant before.

I haven't had treatment for another cancer, except for certain skin, prostate cancers, or early-stage cancers, in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vobramitamab duocarmazine and lorigerlimab on Day 1 of every 4-week cycle for up to 2 years

Up to 2 years

1 visit every 4 weeks

Tumor Assessment

Tumor assessments are performed every 8 weeks for the initial 6 months, then every 12 weeks until progressive disease

6 months to 2 years

Every 8 weeks initially, then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 12 weeks

Treatment Details

Interventions

• Lorigerlimab
• Vobramitamab Duocarmazine

Trial Overview The trial tests vobramitamab duocarmazine (MGC018) in combination with lorigerlimab on patients with various advanced solid tumors. It aims to evaluate safety, tolerability and initial effectiveness of these drugs given every four weeks up to two years unless there's disease progression or unacceptable side effects.

Participant Groups

Group I: Cohort Expansion Experimental Treatment 2 Interventions

maximum tolerated dose of vobramitamab duocarmazine and lorigerlimab IV every 4 weeks

Group II: Cohort 5 Experimental Treatment 2 Interventions

vobramitamab duocarmazine at dose level 4 and lorigerlimab IV every 4 weeks

Group III: Cohort 4 Experimental Treatment 2 Interventions

vobramitamab duocarmazine at dose level 3 and lorigerlimab IV every 4 weeks

Group IV: Cohort 3 Experimental Treatment 2 Interventions

vobramitamab duocarmazine at dose level 2 and lorigerlimab IV every 4 weeks

Group V: Cohort 2 Experimental Treatment 2 Interventions

vobramitamab duocarmazine at dose level 1 and lorigerlimab IV every 4 weeks

Group VI: Cohort 1 Experimental Treatment 2 Interventions

vobramitamab duocarmazine at dose level 1 and lorigerlimab IV every 4 weeks

Group VII: Cohort -1 Experimental Treatment 2 Interventions

vobramitamab duocarmazine at dose level -1 and lorigerlimab intravenously (IV) every 4 weeks

Who Is Running the Clinical Trial?

MacroGenics

Lead Sponsor

Trials

51

Recruited

5,400+

Findings from Research

The investigational bispecific DART molecule MGD019 effectively combines PD-1 and CTLA-4 blockade in a single treatment, showing promise for enhanced therapeutic effects in cancer by targeting tumor-infiltrating lymphocytes.

In a first-in-human study involving patients with advanced solid tumors, MGD019 demonstrated acceptable safety and pharmacodynamic evidence of dual blockade, leading to objective responses in tumor types that usually do not respond to standard checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule. Berezhnoy, A., Sumrow, BJ., Stahl, K., et al.[2022]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

TSAxCD28 bispecific antibodies can enhance the effectiveness of anti-PD-1 therapy, enabling immune responses and long-term memory against tumors that typically do not respond to PD-1 blockers, as demonstrated in preclinical models.

These bispecifics show minimal toxicity compared to other T cell activators, making them a promising and safe addition to cancer immunotherapy regimens, potentially improving outcomes for patients with resistant tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. Waite, JC., Wang, B., Haber, L., et al.[2021]

Bispecific antibodies (BsAbs) have shown clinical effectiveness in treating blood cancers and are now being evaluated for solid tumors, with various BsAb drugs currently in clinical trials targeting specific cancer markers like EpCAM and CEA.

While BsAbs have great potential in cancer treatment, especially for solid tumors, there are still concerns regarding their adverse effects, which need to be addressed in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances and challenges of bispecific antibodies in solid tumors. Wu, Y., Yi, M., Zhu, S., et al.[2021]

In a study involving 478 patients, dostarlimab, an anti-PD-1 monoclonal antibody, showed a low incidence of treatment-emergent antidrug antibodies (ADAs) at 2.5%, indicating a favorable safety profile compared to other similar therapies.

Despite the presence of ADAs in a small number of patients, there was no evidence of reduced efficacy or safety for dostarlimab, supporting its use as an effective treatment for various solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Integrated Analysis of Dostarlimab Immunogenicity. Lu, S., Bowsher, RR., Clancy, A., et al.[2022]

A new bispecific molecule combining an anti-PD-1 antibody with a multimeric GITR ligand enhances T cell activation and memory differentiation, potentially improving cancer immunotherapy outcomes.

In mouse models, this bispecific approach showed dose-dependent tumor growth inhibition, indicating that it effectively targets and activates GITR+PD-1+ T cells to combat tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-PD-1-GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy. Chan, S., Belmar, N., Ho, S., et al.[2022]

The bispecific antibody described in patent US2019161548 targets both PD-1 and CTLA-4, which are important immune checkpoints in cancer, and has been shown to enhance the activation and proliferation of CD8+ T cells and stimulate CD4+ T cells.

Clinical trials are currently underway to assess the safety and effectiveness of this bispecific antibody, with hopes that it may outperform the existing combination therapy of nivolumab and ipilimumab in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific anti-PD-1/CTLA-4 antibody for advanced solid tumors. Perez-Santos, M.[2021]

References

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

Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule. [2022]

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

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

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

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. [2021]

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

Bispecific antibodies in cancer immunotherapy. [2020]

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

A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Recent advances and challenges of bispecific antibodies in solid tumors. [2021]

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

An Integrated Analysis of Dostarlimab Immunogenicity. [2022]

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

An anti-PD-1-GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy. [2022]

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

Bispecific anti-PD-1/CTLA-4 antibody for advanced solid tumors. [2021]