Lorigerlimab + Docetaxel for Prostate Cancer

Not currently recruiting at 64 trial locations

Overseen By Global Trial Manager

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: MacroGenics

Must be taking: ARAT, PARP inhibitors

Must not be taking: Chemotherapy, Checkpoint inhibitors

Disqualifiers: Infections, Heart disorders, 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: 12

Duration: Up to 21 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments to determine if it can slow the progression of advanced prostate cancer that has spread and no longer responds to standard hormone therapy. The trial compares the effectiveness of adding lorigerlimab (an experimental treatment) to the usual treatment of docetaxel (a chemotherapy drug) and prednisone against using just the standard treatment. Men with metastatic castration-resistant prostate cancer (advanced prostate cancer that continues to spread despite hormone treatment) who have already tried other specific therapies might qualify for this study. The goal is to determine if lorigerlimab can help delay cancer progression. Participants will receive treatments through IV and pills, with regular health check-ups and scans to monitor progress. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to important advancements in cancer therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, if you are on androgen receptor axis-targeted therapy or a PARP inhibitor, you must have already shown disease progression after these treatments to be eligible.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study doctor to understand how your current medications might interact with the trial treatments.

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

Research has shown that lorigerlimab, a new treatment, has been tested in people with various cancers. In a study with 127 patients, researchers administered lorigerlimab at a dose similar to what will be used in the current trial. Most participants tolerated the treatment well. Common side effects included tiredness and nausea, but these were usually mild. A few patients experienced more serious side effects, though these were less common.

The standard treatment being tested, docetaxel with prednisone, has been used for prostate cancer for some time. Patients often experience side effects like hair loss and low blood cell counts, but doctors manage these well-known effects.

Overall, early research on lorigerlimab suggests it can be safely given to patients, though like all treatments, it carries some risks. Since this study is in an intermediate phase, the treatment has shown some safety in earlier studies but is still undergoing further testing. ^{1 2 3 4 5}

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

Researchers are excited about Lorigerlimab because it brings a new approach to prostate cancer treatment. Unlike standard treatments that use chemotherapy drugs like docetaxel and prednisone, Lorigerlimab is a monoclonal antibody that targets specific proteins on cancer cells, potentially enhancing the immune system's ability to fight the disease. This targeted action may offer improved efficacy and reduced side effects compared to traditional chemotherapy, providing a promising new option for patients.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that lorigerlimab, when combined with docetaxel, may slow the spread of advanced prostate cancer that no longer responds to hormone therapy. Lorigerlimab targets two proteins, PD-1 and CTLA-4, which help control the immune system. Early studies have found that this combination can enhance the body's ability to fight cancer cells. In this trial, one group of participants will receive both lorigerlimab and docetaxel, while another group will receive only docetaxel with prednisone. Initial results suggest that patients receiving both lorigerlimab and docetaxel may experience slower disease progression compared to those receiving only docetaxel. These findings offer hope for better treatment outcomes in advanced prostate 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 men with advanced prostate cancer that's resistant to hormone therapy and has spread. They should have tried at least one but no more than two previous treatments targeting the androgen receptor, like abiraterone or enzalutamide. If they have a BRCA mutation, they must have been treated with PARP inhibitors. Participants need to be in good physical condition with a decent life expectancy and acceptable lab results.

Inclusion Criteria

My cancer progressed after treatment with hormone therapy.

Participants must have adequate performance status, life expectancy and laboratory values

I have a BRCA mutation and have been treated with a PARP inhibitor.

Exclusion Criteria

Allergy to any of the study treatments or components of the study treatments

Any condition preventing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures

I have had chemotherapy for advanced prostate cancer or immunotherapy for any stage of prostate cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lorigerlimab with docetaxel and prednisone or docetaxel and prednisone alone. Lorigerlimab is administered for up to 35 cycles, and docetaxel and prednisone for up to 10 cycles.

Up to 21 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with regular testing for disease progression using CT scans, MRI, and PSA blood tests.

Up to 4 years

Every 9 weeks for the first year, then every 12 weeks

Open-label extension (optional)

Participants in the standard-of-care arm with disease progression have the option to continue receiving lorigerlimab monotherapy.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Lorigerlimab
• Prednisone

Trial Overview The study is testing if adding Lorigerlimab to the standard treatment of Docetaxel and Prednisone can slow down cancer progression in metastatic castration-resistant prostate cancer patients. Patients will be randomly assigned (2:1) to either receive this combination or just Docetaxel and Prednisone.

How Is the Trial Designed?

Group I: Standard of care docetaxel and prednisone Experimental Treatment 2 Interventions

Docetaxel 75 mg/m\^2 IV every 3 weeks and prednisone 5 mg orally twice daily.(up to 7 months)

Group II: Lorigerlimab + Docetaxel and Prednisone Experimental Treatment 3 Interventions

Lorigerlimab 6 mg/kg IV (up to 2 years) and docetaxel 75 mg/m\^2 IV every 3 weeks (up to 7 months) and prednisone 5 mg orally twice daily (up to 7 months).

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

MacroGenics

Lead Sponsor

Trials

51

Recruited

5,400+

Published Research Related to This Trial

In a study of 1,006 patients, docetaxel combined with prednisone showed a significant overall survival advantage compared to mitoxantrone plus prednisone, with a median survival of 18.9 months versus 16.5 months.

The most common side effects of docetaxel included anemia, neutropenia, and nausea, indicating that while effective, the treatment does come with notable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: Docetaxel in combination with prednisone for the treatment of androgen-independent hormone-refractory prostate cancer. Dagher, R., Li, N., Abraham, S., et al.[2018]

In the TAX-327 study involving 1,006 men with metastatic hormone-refractory prostate cancer, it was found that men with minimal symptoms had a significantly longer median survival of 25.6 months compared to 17.1 months for symptomatic patients, highlighting the importance of symptom management in treatment outcomes.

Both pain response and prostate-specific antigen (PSA) response were independently associated with survival, but quality of life (QoL) response was not, indicating that while pain and PSA levels are important, they should not be solely relied upon as indicators of treatment success in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hormone-refractory prostate cancer with docetaxel or mitoxantrone: relationships between prostate-specific antigen, pain, and quality of life response and survival in the TAX-327 study. Berthold, DR., Pond, GR., Roessner, M., et al.[2022]

In a study of 52 Japanese men with metastatic castration-resistant prostate cancer (mCRPC), receiving 10 or more cycles of docetaxel significantly improved overall survival, with a median survival of 28.5 months compared to 11.2 months for those receiving fewer than 10 cycles.

The study also validated a risk group classification based on factors like anemia and bone metastases, showing that patients in the good risk group had a significantly better overall survival compared to those in intermediate and poor risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for metastatic castration-resistant prostate cancer (CRPC) predict long-term treatment with docetaxel. Kawahara, T., Miyoshi, Y., Sekiguchi, Z., et al.[2022]

Cabazitaxel significantly improves overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) compared to mitoxantrone, with a median survival of 15.1 months versus 12.7 months, indicating its efficacy as a treatment option.

The safety profile of cabazitaxel is similar to that of first-generation taxanes, with manageable side effects such as diarrhea and neutropenia, which can be addressed through monitoring and supportive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cabazitaxel--a next-generation taxane for the treatment of patients with metastatic castration-resistant prostate cancer]. Ecstein-Fraisse, E., Su, Z.[2014]

Abiraterone is considered a cost-effective treatment for metastatic castration-resistant prostate cancer (mCRPC) at $94,000 per quality-adjusted life year (QALY) compared to placebo, based on a decision-tree model analyzing various treatment options over 18 months.

Cabazitaxel, while effective, is not cost-effective compared to abiraterone, with an incremental cost-effectiveness ratio of $956,000 per QALY, indicating that it may not be a viable option for patients after docetaxel failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic options in docetaxel-refractory metastatic castration-resistant prostate cancer: a cost-effectiveness analysis. Zhong, L., Pon, V., Srinivas, S., et al.[2023]

In a study of 83 Chinese patients with metastatic hormone-refractory prostate cancer, docetaxel plus prednisone showed a higher efficacy compared to mitoxantrone plus prednisone, with 43.2% of patients achieving a complete or partial response versus 33.3% for mitoxantrone.

Docetaxel plus prednisone also provided better PSA control, with an average time to PSA progression of 37.8 weeks compared to 25.3 weeks for mitoxantrone, although it was associated with slightly higher toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel plus prednisone versus mitoxantrone plus prednisone for metastatic hormone-refractory prostate cancer in Chinese patients: experience of a single center. Zhang, HL., Ye, DW., Yao, XD., et al.[2018]

In a phase II trial involving 84 patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), the combination of nivolumab and docetaxel showed a confirmed objective response rate (ORR) of 40% and a prostate-specific antigen response rate (PSA50-RR) of 46.9%.

The treatment demonstrated median radiographic progression-free survival (rPFS) of 9 months and overall survival (OS) of 18.2 months, with safety profiles consistent with the individual drugs, although there were three treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer: results from the phase II CheckMate 9KD trial. Fizazi, K., González Mella, P., Castellano, D., et al.[2023]

Docetaxel-based therapy has been shown to provide a survival benefit for men with metastatic prostate cancer, marking a significant advancement beyond palliative care options.

Ongoing trials are exploring various combination therapies with docetaxel, but the best timing for initiating treatment remains unclear due to a lack of prospective clinical trial data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role of chemotherapy in metastatic hormone-refractory prostate cancer. Petrylak, DP.[2022]

The Tax 327 Phase III study demonstrated that docetaxel-based chemotherapy significantly improves overall survival in patients with androgen-insensitive metastatic prostate cancer compared to the previously used mitoxantrone and prednisone, marking a breakthrough in treatment efficacy.

This study is particularly important as it is the first adequately powered trial to show a definitive survival benefit for this patient group, paving the way for future research into combination therapies with docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel-based regimens, the standard of care for metastatic androgen-insensitive prostate cancer. Arlen, PM., Gulley, JL.[2018]

In a study of 1006 patients with metastatic hormone-refractory prostate cancer, those who crossed over to receive second-line therapy after initial treatment showed a median survival of 10 months, regardless of the order of treatments.

The response rate for prostate-specific antigen (PSA) reduction was higher in patients receiving docetaxel after mitoxantrone (28%) compared to those receiving mitoxantrone after docetaxel (15%), indicating a potential advantage for the sequence of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival and PSA response of patients in the TAX 327 study who crossed over to receive docetaxel after mitoxantrone or vice versa. Berthold, DR., Pond, GR., de Wit, R., et al.[2020]

Docetaxel chemotherapy is a standard first-line treatment for castration-resistant prostate cancer, providing a modest overall survival benefit of 2 months, but patients typically progress to a docetaxel-insensitive phase within 6-9 months.

Emerging therapies like cabazitaxel, sipuleucel-T, and abiraterone show promise for secondary treatment options, highlighting the need for more clinical data to explore various combinations and sequences of therapies for better outcomes in specific patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Second line therapy for castration-resistant prostate cancer (CRPC)]. Molitor, B., Börgermann, C.[2021]

Docetaxel is the first treatment to significantly improve survival rates in patients with hormone-refractory prostate cancer, and it is now being tested in earlier stages of the disease to prevent recurrence in high-risk patients.

Pilot studies indicate that using docetaxel as a neo-adjuvant treatment can be done safely without increasing surgical risks, and ongoing randomized trials will further assess its effectiveness when combined with hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-risk localized prostate cancer: integrating chemotherapy. Oh, WK.[2018]

Citations

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

Lorigerlimab (PD-1 × CTLA-4) Lorigerlimab (previously known as MGD019) is an investigational, bispecific DART molecule that targets PD-1 and CTLA-4.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.TPS242

LORIKEET: A phase 2, randomized, open-label study of ... The phase 2 LORIKEET study will compare the combination of lorigerlimab plus docetaxel versus docetaxel alone in patients with mCRPC.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05848011

NCT05848011 | A Study of Lorigerlimab With Docetaxel or ... The purpose of this study is to determine whether the amount of time before disease progression can be prolonged in participants with metastatic ...

4. macrogenics.com macrogenics.com/wp-content/uploads/2025/04/2-16-23-ASCO-GU-2023-Luke-et-al.-Lorigerlimab-Dose-Expansion-mCRPC-2023-02-16.pdf

Lorigerlimab, a Bispecific PD-1 × CTLA-4 DART® Molecule ... Metastatic Castration-Resistant Prostate Cancer Expansion Cohort Results ... • Preliminary efficacy results for the mCRPC cohort are.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03761017

MGD019 DART® Protein in Unresectable/Metastatic Cancer The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT395074

Lorigerlimab, a bispecific PD-1×CTLA-4 DART molecule in ... Results: At data cutoff (9/10/22), 127 pts with AST received ≥1 dose of lorigerlimab 6 mg/kg. Median exposure was 10 weeks (range, 0.1, 94.4) with median ...