Lorigerlimab for Ovarian Cancer

Recruiting at 25 trial locations

Overseen By Global Trial Manager

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: MacroGenics

Must not be taking: Checkpoint inhibitors

Disqualifiers: Brain metastases, Transplant, Refractory disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Until progression of cancer or unacceptable side effects

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called lorigerlimab for individuals with ovarian cancer that no longer responds to standard platinum-based chemotherapy or for those with clear cell gynecologic cancer. The trial aims to evaluate the effectiveness and safety of lorigerlimab for these conditions. Participants will receive the treatment through an IV every 21 days, with doctors closely monitoring for side effects and changes in tumor size. This trial may suit individuals with ovarian or clear cell gynecologic cancer who have not had success with previous treatments and are in generally good physical condition. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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 lorigerlimab is likely to be safe for humans?

Research has shown that lorigerlimab effectively fights tumors and is generally safe. This treatment enhances the body's immune response against cancer by targeting two proteins that typically allow cancer to evade detection.

Earlier research indicated that most patients tolerated lorigerlimab well, experiencing no severe side effects. However, some side effects may occur, and healthcare providers closely monitor them.

Overall, evidence suggests that lorigerlimab is safe, with manageable side effects for most patients. Prospective trial participants should discuss any concerns with the study team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Unlike the standard treatments for ovarian cancer, which often include chemotherapy and targeted therapies, Lorigerlimab is a novel monoclonal antibody. Researchers are excited about Lorigerlimab because it targets specific proteins on cancer cells more precisely, potentially leading to fewer side effects compared to traditional chemotherapy. Additionally, Lorigerlimab's unique mechanism of action might enhance the immune system's ability to recognize and attack ovarian cancer cells, offering a promising new approach for patients.

What evidence suggests that lorigerlimab might be an effective treatment for ovarian cancer?

Research has shown that lorigerlimab could be a promising treatment for certain cancers. Lorigerlimab is a special type of protein that targets two cancer-related proteins, PD-1 and CTLA-4, to help the immune system fight cancer cells. In studies on other cancers, lorigerlimab slowed disease progression. This trial will evaluate lorigerlimab in two separate cohorts: one for platinum-resistant ovarian cancer and another for clear cell gynecologic cancer. Researchers aim to see if it offers similar benefits in these specific cancers. Early research on different cancers suggests that lorigerlimab might help patients who have already tried other treatments. While more information is needed specifically for ovarian and gynecologic cancers, its mechanism supports its potential effectiveness. ^{1 5 6 7 8}

Who Is on the Research Team?

Pepi Pencheva

Principal Investigator

MacroGenics

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors, including ovarian, endometrial, cervical, vaginal, vulvar and uterine cancers that are resistant to platinum-based chemotherapy. They must have had a limited number of prior treatments and not be pregnant or breastfeeding. Participants need measurable disease by RECIST v1.1 criteria and acceptable health status.

Inclusion Criteria

Participants must not be pregnant, planning to be pregnant, or breastfeeding

Participants must have at least one lesion that meets the definition of measurable disease by RECIST v1.1

Participants of childbearing potential must agree to use highly effective methods of birth control

Exclusion Criteria

Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures

I have had a stem cell, tissue, or organ transplant in the past.

I have been treated with a checkpoint inhibitor before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lorigerlimab by intravenous (IV) infusion on Day 1 of every 21-day treatment cycle

Until progression of cancer or unacceptable side effects

1 visit every 21 days (in-person)

Monitoring

Participants are monitored for side effects and tumor status is checked approximately every 9 weeks for the first year, then every 12 weeks

Throughout treatment

Follow-up

Participants have a safety follow-up performed within 30 days after treatment discontinuation

30 days

Survival Follow-up

Participants who discontinue study treatment for progression of cancer will enter the 6-month survival follow-up portion of the study

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Lorigerlimab

Trial Overview The study tests Lorigerlimab in patients with specific gynecologic cancers resistant to standard treatments. It's an open-label trial where all participants receive the drug via IV every three weeks until their cancer progresses or side effects become too severe.

How Is the Trial Designed?

Group I: PROC Cohort Experimental Treatment 1 Intervention

Lorigerlimab IV every 21 days

Group II: CCGC Cohort Experimental Treatment 1 Intervention

Lorigerlimab IV every 21 days

Who Is Running the Clinical Trial?

MacroGenics

Lead Sponsor

Trials

51

Recruited

5,400+

Published Research Related to This Trial

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

Immune checkpoint inhibitors, which target specific proteins like CTLA-4 and PD-1, have significantly improved survival rates for patients with advanced solid tumors, including ovarian cancer.

The report emphasizes the need for early recognition and management of immune-related adverse events, which differ from those seen with traditional chemotherapy, highlighting the unique challenges of immunotherapy in treating gynecologic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and Management of Immune Checkpoint Inhibitor-related Toxicities in Ovarian Cancer: A Series of Case Vignettes. Johnson, C., Jazaeri, AA.[2019]

In a study of 44 women with recurrent ovarian cancer treated with immune checkpoint inhibitors, the overall response rate was 14.2%, with a notable correlation between platinum sensitivity and response in high-grade serous ovarian cancer (HGSOC) patients.

Severe immune-related adverse events (irAEs) occurred in 47.7% of patients, with elevated hepatic or pancreatic enzymes being the most common, and a higher number of gene mutations appeared to protect against these specific adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials. Hinchcliff, E., Hong, D., Le, H., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06730347

NCT06730347 | A Study of Lorigerlimab in Participants ... The study will assess the efficacy and safety of lorigerlimab in participants with PROC or CCGC. Participants will receive lorigerlimab by intravenous (IV) ...

2. macrogenics.com macrogenics.com/news/macrogenics-provides-update-on-corporate-progress-and-first-quarter-2025-financial-results/

MacroGenics Provides Update on Corporate Progress and ... Notably, we dosed the first patient in our Phase 2 LINNET study of lorigerlimab, which will evaluate patients with platinum-resistant ovarian ...

3. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/MGNX-Q/pressreleases/35742334/macrogenics-lorigerlimab-study-a-potential-game-changer-in-cancer-treatment/

MacroGenics' Lorigerlimab Study: A Potential Game- ... ' The study aims to assess the efficacy and safety of lorigerlimab, a bispecific DART protein, in patients with platinum-resistant ovarian ...

4. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2024-2001.html

A phase 2 multicohort study to evaluate lorigerlimab in ... The study will assess the efficacy and safety of lorigerlimab in participants with PROC or CCGC. Participants will receive lorigerlimab by intravenous (IV) ...

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

Lorigerlimab, a bispecific PD-1×CTLA-4 DART molecule in ... There were no fatal AEs related to lorigerlimab. In the mCRPC exp cohort (n=42), pts had a median of 2 prior lines of therapy for CRPC, >80% ...

6. medchemexpress.com medchemexpress.com/lorigerlimab.html?srsltid=AfmBOopOhBYoHPToGxTZoXFyjLTRdYbmYW7d3YzF89Qd26SQjvi8VnPb

Lorigerlimab (MGD019) | PD-1/CTLA-4 DART Lorigerlimab (MGD019) is a bispecific IgG4 dual-affinity re-targeting antibody (DART). Lorigerlimab can block PD-1 and CTLA-4, and improves T-cell responses.

7. sec.gov sec.gov/Archives/edgar/data/1125345/000112534525000054/exhibit99-1earningspressre.htm

99.1 Lorigerlimab is a bispecific, tetravalent PD-1 × CTLA-4 DART® molecule designed to enhance CTLA-4 blockade on dual-expressing, tumor-infiltrating lymphocytes ...

8. oncologypipeline.com oncologypipeline.com/apexonco/macrogenics-cuts-down-its-tamarack

MacroGenics cuts down its Tamarack | ApexOnco ... lorigerlimab in ovarian cancer. This will test a 6mg/kg thrice-weekly dose, investigate response rates as primary endpoint, and start by mid ...