MGC018 + MGD019 for Solid Tumors

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, vobramitamab duocarmazine and lorigerlimab (also known as MGD019), for individuals with certain advanced solid tumors, such as prostate, melanoma, and pancreatic cancers. The main goal is to assess the safety and tolerability of these treatments and their potential to reduce tumor size. Participants will receive the treatments every four weeks and undergo regular tumor evaluations. The trial seeks individuals who have tried other approved therapies but still have advanced cancer that cannot be removed or has spread. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these new treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vobramitamab duocarmazine may help treat certain cancers, such as advanced prostate cancer. Previous studies indicate that most patients tolerated the drug well, although some experienced side effects. These studies suggest the drug could be effective, but more research is needed to fully understand its safety.

Lorigerlimab is another experimental drug designed to fight cancer by targeting specific proteins. Early studies have examined its safety and patient tolerance. While these studies provide some information, researchers are still learning about all its possible effects.

Keep in mind, this is a Phase 1 study, which primarily focuses on safety and determining the right dose. The treatment is still in the early stages of testing in people, so there may still be unknowns about its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about lorigerlimab and vobramitamab duocarmazine because these treatments offer a novel approach for fighting solid tumors. Unlike traditional chemotherapy, which attacks rapidly dividing cells in a more generalized way, vobramitamab duocarmazine is an antibody-drug conjugate that targets tumor cells specifically, potentially minimizing damage to healthy cells. Lorigerlimab, on the other hand, harnesses the power of immunotherapy by engaging the immune system to recognize and attack cancer cells more effectively. Together, these treatments could provide a more targeted and potentially less toxic option than the current standard of care for solid tumors.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that vobramitamab duocarmazine has promising effects in fighting advanced cancers. Studies have observed significant tumor shrinkage in various conditions, including advanced prostate cancer. This treatment targets B7-H3, a protein commonly found in solid tumors, making it a hopeful option for treating hard-to-treat cancers.

In this trial, participants will receive vobramitamab duocarmazine at different dose levels alongside lorigerlimab, a special type of antibody that blocks PD-1 and CTLA-4, proteins that cancer cells use to hide from the immune system. By blocking these proteins, lorigerlimab helps the immune system better recognize and attack cancer cells. Early research suggests that lorigerlimab can benefit different types of cancer, especially when used with other treatments. Together, these treatments aim to boost the body's ability to fight cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Denise Casey, M.D.

Principal Investigator

MacroGenics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.155

Lorigerlimab, a bispecific PD-1×CTLA-4 DART molecule in ... Lorigerlimab (MGD019) is an investigational, bispecific Fc-bearing (IgG4) DART molecule designed to enhance CTLA-4 blockade on dual expressing, tumor ...

2. macrogenics.com macrogenics.com/pipeline/mgd019-pd-1-x-ctla-4/

Lorigerlimab (PD-1 × CTLA-4) Lorigerlimab was designed to enhance CTLA-4 blockade on dual-expressing, tumor-infiltrating lymphocytes compared to a PD-1/CTLA-4 monoclonal antibody (mAb) ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7762776/

Development and Preliminary Clinical Activity of PD-1-Guided ... Combination immunotherapy with antibodies directed against PD-1 and CTLA-4 shows improved clinical benefit across cancer indications ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)41136-6/fulltext

1020O A phase I, first-in-human, open-label, dose ... This study characterizes safety, tolerability, dose-limiting toxicities, maximum tolerated dose (MTD), PK/PD, and preliminary antitumor activity of MGD019 in ...

5. onclive.com onclive.com/view/dart-molecule-mgd019-displays-monotherapy-efficacy-in-heavily-pretreated-solid-tumors

DART Molecule MGD019 Displays Monotherapy Efficacy in ... “Dual blockade of PD-1 and CTLA-4 as a monoclonal combination has been a successful strategy yielding improved efficacy in multiple tumor types.

6. clin.larvol.com clin.larvol.com/trial-detail/NCT03761017

MGD019 DART® Protein in Unresectable/Metastatic Cancer A Phase I, first-in-human, open label, dose-escalation and cohort expansion study of MGD019, a bispecific DARTprotein binding PD-1 and CTLA-4 in patients with ...