Lorigerlimab for Ovarian Cancer

Recruiting at 17 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

Trial Summary

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 safety data exists for immune checkpoint inhibitors in ovarian cancer treatment?

Immune checkpoint inhibitors, used in treating various cancers including ovarian cancer, can cause immune-related side effects, which are different from those seen with traditional chemotherapy. It's important to recognize and manage these side effects early to ensure patient safety. ^{1 2 3 4 5}

How is the drug Lorigerlimab different from other ovarian cancer treatments?

Lorigerlimab is unique because it is an immunotherapy, which means it works by helping the body's immune system fight the cancer. This approach is different from traditional treatments like chemotherapy, which directly target and kill cancer cells. ^{6 7 8 9 10}

What is the purpose of this trial?

Study CP-MGD019-03 is an open-label study of lorigerlimab in participants with platinum-resistant ovarian cancer (PROC) or clear cell gynecologic cancer (CCGC). Approximately 60 participants will be enrolled. The study will assess the efficacy and safety of lorigerlimab in participants with PROC or CCGC. Participants will receive lorigerlimab by intravenous (IV) infusion on Day 1 of every 21-day treatment cycle. Treatment cycles will continue until progression of cancer, unacceptable side effects, withdrawal of consent by the participant, or the study ends. Participants will be monitored closely for side effects by physical exam and routine laboratory tests every cycle. Tumor status will be checked approximately every 9 weeks for the first year, then every 12 weeks for the duration of treatment. Participants will have a safety followup performed within 30 days after treatment discontinuation. Participants who discontinue study treatment for reasons other than progression of cancer, will continue CA-125 and tumor assessments every 12 weeks. Participants who discontinue study treatment for progression of cancer will enter the 6-month survival follow up portion of the study.

Research Team

Pepi Pencheva

Principal Investigator

MacroGenics

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The Latest Findings of PD-1/PD-L1 Inhibitor Application in Gynecologic Cancers. [2021]

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

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials. [2023]

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

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

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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

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

The role of immune checkpoint inhibition in the treatment of ovarian cancer. [2022]

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

Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial. [2022]

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

Immune checkpoint blockade reveals the stimulatory capacity of tumor-associated CD103(+) dendritic cells in late-stage ovarian cancer. [2021]

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

Treatment of ovarian clear cell carcinoma with immune checkpoint blockade: a case series. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy in Ovarian Cancer: Thinking Beyond PD-1/PD-L1. [2021]

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

Single-cell transcriptomics identify TNFRSF1B as a novel T-cell exhaustion marker for ovarian cancer. [2023]