Lorigerlimab for Advanced Solid Tumors

No longer recruiting at 44 trial locations

Overseen By Johanna Bendell, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MacroGenics

Must not be taking: Monoclonal antibodies

Disqualifiers: Symptomatic CNS metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 18

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests lorigerlimab, a new treatment for individuals with advanced solid tumors that cannot be surgically removed or have spread. Lorigerlimab is a PD-1 x CTLA-4 bispecific DART molecule, a type of immunotherapy designed to help the immune system combat cancer. The main goal is to assess the treatment's safety and effectiveness against cancer. The study evaluates different doses to determine the safest amount that remains effective against tumors. Suitable candidates include those with specific cancers, such as colorectal cancer or melanoma, who have not responded to other treatments. As a Phase 1 trial, this research aims to understand how lorigerlimab works in people, offering participants the chance to be among the first to receive this innovative treatment.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking any systemic cancer treatments or investigational therapies at least 4 weeks before starting the study drug. If you are taking radiation therapy, you need to stop it 2 weeks before starting the study drug. For certain prostate cancer treatments, a 6-month gap is required.

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

Research shows that lorigerlimab, also known as MGD019, is being tested for safety in individuals with advanced solid tumors. This treatment aims to block two proteins, PD-1 and CTLA-4, to enhance the immune system's ability to fight cancer.

In earlier studies, patients received varying doses of lorigerlimab to determine the safest and most effective amount. These studies assessed side effects and patient tolerance, helping researchers understand potential risks and benefits.

As a Phase 1 study, the primary goal is to evaluate the treatment's safety in humans. This phase typically marks the first time the drug is tested in people, focusing on safety and potential side effects.

Although long-term safety information is not yet available, the fact that this treatment is being studied in humans suggests promising results from earlier lab tests. The safety of lorigerlimab remains under evaluation, with researchers closely monitoring for any adverse effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Lorigerlimab because it offers a novel approach to treating advanced solid tumors. Unlike standard treatments, which often focus on specific tumor types, Lorigerlimab targets multiple tumor antigens simultaneously using a bispecific DART® protein technology. This could potentially enhance the immune system's ability to recognize and attack a wider range of cancer cells. Moreover, its administration in varying doses every three weeks allows for flexibility in treatment intensity, which could lead to more personalized therapy plans. These unique features make Lorigerlimab a promising candidate in the fight against difficult-to-treat cancers.

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

Studies have shown that lorigerlimab blocks two proteins, PD-1 and CTLA-4, which help cancer cells evade the immune system. By blocking these proteins, lorigerlimab enables the immune system to better recognize and attack cancer cells. Research indicates that this dual blockade approach can be more effective than targeting a single protein. Initial findings suggest that this treatment offers improved benefits in various types of cancer. This trial will test different dosages of lorigerlimab to determine its effectiveness in helping the immune system combat advanced solid tumors. ^{1 2 3 4 5}

Who Is on the Research Team?

Denise Casey, MD

Principal Investigator

MacroGenics

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that can't be surgically removed or have spread, and who've run out of treatment options or can't handle standard treatments. It's open to those in good physical condition (ECOG 0-1) and includes specific criteria for lung cancer, melanoma, colorectal cancer, and prostate cancer patients.

Inclusion Criteria

My skin cancer worsened after treatment, and I've had PD-1/PD-L1 or CTLA-4 inhibitors.

I have prostate cancer that has worsened despite treatment, with a PSA over 2 ng/mL.

I have a tumor sample available for testing, or I can provide one.

Exclusion Criteria

I have had severe side effects from immune therapy, including eye issues, liver changes, nerve problems, colon inflammation, kidney issues, or lung inflammation.

You have a history of certain autoimmune diseases, unless specified otherwise.

Your testosterone level is higher than 50 ng/dl or 1.7 nmol/L for this specific type of cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation will occur in a 3+3+3 design to determine the maximum tolerated/administered dose (MTD/MAD) of MGD019 in patients with advanced solid tumors.

Varies

Every 3 weeks

Cohort Expansion

Once the MTD/MAD is determined, a Cohort Expansion Phase will be enrolled to further characterize safety and initial anti-tumor activity in patients with specific tumor types.

Varies

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with tumor status assessed every 12 weeks.

Up to 4 years

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lorigerlimab
• MGD019 DART® Protein

Trial Overview The study tests Lorigerlimab's safety and how the body processes it. Initially, small groups will receive increasing doses to find the highest dose that doesn’t cause serious side effects. Then more people with certain types of cancer will join to see if the drug effectively fights their tumors.

How Is the Trial Designed?

Group I: Cohort 7 Experimental Treatment 1 Intervention

10.0 mg/kg administered IV every 3 weeks.

Group II: Cohort 6 Experimental Treatment 1 Intervention

6.0 mg/kg administered IV every 3 weeks.

Group III: Cohort 5 Experimental Treatment 1 Intervention

30\. mg/kg administered IV every 3 weeks.

Group IV: Cohort 4 Experimental Treatment 1 Intervention

1.0 mg/kg administered IV every 3 weeks.

Group V: Cohort 3 Experimental Treatment 1 Intervention

0.3 mg/kg administered IV every 3 weeks.

Group VI: Cohort 2 Experimental Treatment 1 Intervention

0.1 mg/kg administered IV every 3 weeks.

Group VII: Cohort 1 Experimental Treatment 1 Intervention

0.03 mg/kg administered IV every 3 weeks.

Who Is Running the Clinical Trial?

MacroGenics

Lead Sponsor

Trials

51

Recruited

5,400+

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. macrogenics.com macrogenics.com/wp-content/uploads/2023/03/ESMO-2020-MGD019-PD-1-x-CTLA-4-Phase-1-Dose-Escalation-Oral-Presentation-1.pdf

ESMO-2020-MGD019-PD-1-x-CTLA-4-Phase-1-Dose- ... PD-1 and CTLA-4 are checkpoint molecules with complementary mechanisms of action. • Dual blockade has yielded enhanced efficacy with approved agents, ...

4. 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 ...

5. 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 ...