Lorigerlimab + Docetaxel for Prostate Cancer

Recruiting at 60 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

154 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding lorigerlimab to standard treatments (docetaxel and prednisone) can slow down prostate cancer that has spread and is not responding to hormone therapy. Lorigerlimab helps the immune system fight cancer, while docetaxel kills cancer cells, and prednisone manages side effects. About 150 patients will participate, with some receiving the new combination and others receiving just the standard treatment.

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.

What data supports the idea that Lorigerlimab + Docetaxel for Prostate Cancer is an effective treatment?

The available research shows that docetaxel, when used with prednisone, has been proven to improve survival in patients with metastatic hormone-refractory prostate cancer. The TAX-327 study demonstrated that patients receiving docetaxel had better survival and symptom control compared to those receiving mitoxantrone. This suggests that docetaxel is an effective component of treatment for this type of prostate cancer. Although specific data on Lorigerlimab combined with docetaxel is not provided, the effectiveness of docetaxel in improving survival rates supports the potential effectiveness of the combination treatment. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Lorigerlimab + Docetaxel for prostate cancer?

Research shows that docetaxel, when combined with prednisone, improves survival in patients with metastatic hormone-refractory prostate cancer, as demonstrated in the TAX-327 study. This suggests that docetaxel is effective in treating advanced prostate cancer, and combining it with other drugs like Lorigerlimab may enhance its benefits. ^{1 2 3 4 5}

What safety data exists for Lorigerlimab + Docetaxel treatment in prostate cancer?

The safety data for Docetaxel, often combined with Prednisone, is well-documented in the treatment of metastatic hormone-refractory prostate cancer. The TAX-327 study and other trials have evaluated its efficacy and adverse events, showing it can extend survival. Docetaxel has been approved by the FDA for this use since 2004. However, specific safety data for Lorigerlimab (MGD019) combined with Docetaxel is not detailed in the provided research, suggesting that further studies may be needed to evaluate this combination. ^{1 2 4 6 7}

Is the combination of Lorigerlimab and Docetaxel safe for humans?

Docetaxel, often used with prednisone, has been approved for treating prostate cancer and has been studied for safety in various trials. Common side effects include low blood cell counts, fatigue, and nausea, but it is generally considered safe when monitored by healthcare professionals. ^{1 2 4 6 7}

Is the drug combination of Docetaxel, Lorigerlimab, and Prednisone promising for prostate cancer?

Yes, the combination is promising because Docetaxel is known to improve survival in prostate cancer patients and has immunostimulatory effects, which can enhance the body's immune response against cancer. Combining it with other drugs like Lorigerlimab could potentially boost its effectiveness. ^{8 9 10 11 12}

What makes the drug combination of Lorigerlimab, Docetaxel, and Prednisone unique for prostate cancer?

This drug combination is unique because it includes Lorigerlimab, a bispecific DART molecule targeting both PD-1 and CTLA-4, which may enhance the immune response against prostate cancer cells when combined with Docetaxel, a chemotherapy drug known for its immunostimulatory effects. ^{8 9 10 11 12}

Research Team

Denise Casey, M.D.

Principal Investigator

MacroGenics

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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]

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 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]

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]

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]

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]

References

1. United States 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. [2022]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

Approval summary: Docetaxel in combination with prednisone for the treatment of androgen-independent hormone-refractory prostate cancer. [2018]

5. England 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. [2020]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Switzerland 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. [2018]

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

Risk factors for metastatic castration-resistant prostate cancer (CRPC) predict long-term treatment with docetaxel. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

[Second line therapy for castration-resistant prostate cancer (CRPC)]. [2021]

10. England 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. [2023]

11. Japan pubmed.ncbi.nlm.nih.gov

[Cabazitaxel--a next-generation taxane for the treatment of patients with metastatic castration-resistant prostate cancer]. [2014]

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

Therapeutic options in docetaxel-refractory metastatic castration-resistant prostate cancer: a cost-effectiveness analysis. [2023]