LAVA-1207 for Prostate Cancer

Recruiting at 12 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Lava Therapeutics

Must be taking: Androgen deprivation therapy

Must not be taking: Aminobisphosphonates, Immunosuppressants

Disqualifiers: Other malignancies, Uncontrolled conditions, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days for initial dose-limiting toxicity assessment, followed by approximately 24 months

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests new treatments for advanced prostate cancer that doesn't respond to standard treatments. The treatments include a new drug, an immune system booster, and a medication that helps the immune system fight cancer.

Do I have to stop taking my current medications for the LAVA-1207 trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had certain treatments like antitumor therapies, systemic chemotherapy, or targeted immunotherapy within 2 to 4 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have had certain cancer treatments or investigational drugs within a few weeks before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the idea that LAVA-1207 for Prostate Cancer is an effective treatment?

The available research does not provide specific data on the effectiveness of LAVA-1207 for prostate cancer. Instead, it discusses other treatments like Pembrolizumab, IMM-101, Radium-223, and Sipuleucel-T. Among these, IMM-101 showed the highest average survival time of 56 months, while Sipuleucel-T demonstrated a 4.1-month improvement in survival compared to a control group. Without specific data on LAVA-1207, it's unclear how it compares to these treatments. ^{1 2 3 4 5}

What safety data is available for LAVA-1207 in prostate cancer treatment?

The provided research does not contain any safety data specifically for LAVA-1207 or its variants. The studies focus on radium-223 dichloride and marimastat, which are different treatments for prostate cancer. ^{6 7 8 9 10}

Is the treatment LAVA-1207 a promising treatment for prostate cancer?

The information provided does not directly mention LAVA-1207, but it highlights the promise of similar treatments like Lutetium-177 PSMA for prostate cancer. These treatments have shown favorable outcomes, improved quality of life, and are considered promising for patients with advanced prostate cancer. ^{11 12 13 14 15}

Research Team

Clinical Trials Management

Principal Investigator

Lava Therapeutics

Eligibility Criteria

Men over 18 with advanced prostate cancer that hasn't responded to chemotherapy and certain hormone therapies. They must have a life expectancy of at least 6 months, be in fairly good physical condition (ECOG status of 0 or 1), and agree to use effective contraception. Men with active infections, immune disorders, unstable heart conditions, recent bisphosphonate treatment, or substance abuse issues cannot participate.

Inclusion Criteria

I am a man who has had a vasectomy.

I am 18 years old or older.

I am a male with advanced prostate cancer that can be measured or evaluated.

Exclusion Criteria

Known clinically relevant immunodeficiency disorders.

I do not have any ongoing or uncontrolled infections.

My heart condition is unstable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LAVA-1207 alone or with low dose interleukin-2 or Pembrolizumab

28 days for initial dose-limiting toxicity assessment, followed by approximately 24 months

Follow-up

Participants are monitored for safety, tolerability, and antitumor activity, including the evaluation of circulating tumor cells and DNA

Approximately 24 months

Treatment Details

Interventions

• LAVA-1207

Trial Overview The trial is testing LAVA-1207's safety and how well it works for men whose prostate cancer has spread and resisted previous treatments. This early-phase study will gradually determine the best dose to minimize risks while assessing its effectiveness against the cancer.

Participant Groups

Group I: LAVA-1207 with Low-Dose Subcutaneous IL-2 (LDSC IL-2) Experimental Treatment 1 Intervention

LAVA-1207 with Low-Dose Subcutaneous IL-2 (LDSC IL-2)

Group II: LAVA-1207 plus Pembrolizumab Experimental Treatment 2 Interventions

LAVA-1207 plus Pembrolizumab

Group III: LAVA-1207 Experimental Treatment 1 Intervention

LAVA-1207

Who Is Running the Clinical Trial?

Lava Therapeutics

Lead Sponsor

Trials

2

Recruited

200+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

This systematic review analyzed 24 prostate cancer patients and found that immunotherapies, particularly IMM-101, showed promising results with a mean overall survival (OS) of 56 months, indicating potential benefits for patients.

Among the immunotherapies studied, Pembrolizumab and IMM-101 were the most commonly used, highlighting their relevance in the treatment landscape for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. Ashraf, MU., Farwa, U., Siddiqa, M., et al.[2023]

In a study of 109 men with localized prostate cancer, higher levels of CD8 expression and lower levels of PD-L1 in tumor samples were linked to a lower risk of biochemical recurrence (BCR) and metastasis-free survival (MFS) over a median follow-up of 8.1 years.

Men with low CD8 and/or high PD-L1 had significantly shorter times to BCR and MFS, suggesting that these immune markers could provide important prognostic information for patients after radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between CD8 and PD-L1 expression and outcomes after radical prostatectomy for localized prostate cancer. Vicier, C., Ravi, P., Kwak, L., et al.[2021]

In a study of 134 men with metastatic castration-resistant prostate cancer treated with Radium-223, about 20% experienced PSA flares, but these flares did not negatively impact overall survival, which was similar to those who had PSA responses or non-responses.

The median overall survival for patients experiencing PSA flares was 16.8 months, indicating that PSA response patterns may not be reliable indicators of treatment outcomes with Radium-223, suggesting a need for further research into better markers of response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and Prognostic Implications of PSA Flares during Radium-223 Treatment among Men with Metastatic Castration Resistant Prostate Cancer. Sidhu, A., Khan, N., Phillips, C., et al.[2023]

Sipuleucel-T is the first therapeutic vaccine approved for metastatic castration-resistant prostate cancer (mCRPC) and has shown a significant overall survival benefit with very low toxicity, making it a promising new treatment option.

Despite its benefits, challenges such as understanding its mechanism of action, high cost, and questions about its optimal use in treatment sequences may hinder its widespread adoption among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sipuleucel-T for the treatment of metastatic prostate cancer: promise and challenges. Paller, CJ., Antonarakis, ES.[2016]

Sipuleucel-T treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) leads to significant increases in both CD4+ and CD8+ T-cell proliferation specific to the immunogen PA2024, indicating a robust immune response.

Higher levels of cytotoxic T lymphocyte (CTL) activity specific to PA2024 at 26 weeks post-treatment are associated with improved overall survival, suggesting that the immune response elicited by sipuleucel-T plays a crucial role in its therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigen-Specific CD8 Lytic Phenotype Induced by Sipuleucel-T in Hormone-Sensitive or Castration-Resistant Prostate Cancer and Association with Overall Survival. Antonarakis, ES., Small, EJ., Petrylak, DP., et al.[2020]

In the ALSYMPCA trial involving 600 patients treated with radium-223, the treatment was found to be well tolerated with a low incidence of myelosuppression and no new safety concerns reported up to 3 years after the first injection.

While 94% of radium-223 patients experienced treatment-emergent adverse events, serious hematologic issues were rare, and long-term follow-up showed no cases of acute myelogenous leukemia or myelodysplastic syndrome, indicating a favorable safety profile for radium-223 in treating symptomatic prostate cancer with bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial. Parker, CC., Coleman, RE., Sartor, O., et al.[2022]

Radium-223 ((223)Ra) is an FDA-approved treatment for men with castration-resistant prostate cancer (CRPC) who have symptomatic bone metastases and no known visceral metastatic disease, showing increased survival compared to standard care in clinical trials.

While (223)Ra is generally well tolerated with up to 6 injections, common side effects include nausea, diarrhea, and various blood-related issues, indicating the need for further research on its long-term safety and potential use alongside chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radium-223 dichloride: a novel treatment option for castration-resistant prostate cancer patients with symptomatic bone metastases. McGann, S., Horton, ER.[2019]

In a real-world study of 1465 men with metastatic castration-resistant prostate cancer (mCRPC) receiving radium-223, the treatment demonstrated a median overall survival of 15.6 months, consistent with previous clinical trial results.

The safety profile was favorable, with 21% of patients experiencing serious adverse events during treatment and 15% having significant hematological toxicities within 6 months after therapy, indicating that radium-223 is a viable option in the current treatment landscape.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes and treatment patterns in REASSURE: planned interim analysis of a real-world observational study of radium-223 in metastatic castration-resistant prostate cancer. Higano, CS., George, DJ., Shore, ND., et al.[2023]

In a study of 75 metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223, those who discontinued treatment due to adverse events had significantly worse progression-free survival (PFS) and overall survival (OS) compared to those who stopped for other reasons.

The likelihood of treatment discontinuation due to toxicity was linked to factors such as the number of previous treatments and baseline blood markers, suggesting that early intervention with Ra-223 may help minimize toxicities and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of radium-223 discontinuation due to adverse events in castration-resistant prostate cancer patients. A retrospective monocentric analysis. Turco, F., Tucci, M., Angusti, T., et al.[2023]

Marimastat, when administered at a dose of 20 mg, significantly decreased the rate of prostate-specific antigen (PSA) increase in patients with biochemically relapsed prostate cancer, indicating its potential to delay disease progression.

However, higher doses of marimastat (20 mg and 40 mg) were associated with significant dose-limiting musculoskeletal toxicity, leading to early discontinuation of these doses in the study, highlighting the need for caution in dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marimastat in the treatment of patients with biochemically relapsed prostate cancer: a prospective randomized, double-blind, phase I/II trial. Rosenbaum, E., Zahurak, M., Sinibaldi, V., et al.[2014]

Lutetium 177 prostate-specific membrane antigen 617 (Lu-177 PSMA) therapy is emerging as a promising treatment for metastatic castration-resistant prostate cancer (mCRPC), which is a challenging condition that arises after standard treatments fail.

This endo-radioligand therapy aims to improve disease control and enhance the quality of life for patients suffering from advanced prostate cancer, highlighting its potential as a novel palliative option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Walk with Lu-177 PSMA: How Close we Have Reached from Bench to Bedside? Gupta, M., Karthikeyan, G., Choudhury, PS., et al.[2021]

The ENZA-p trial is investigating the safety and efficacy of combining lutetium-177 (177 Lu)-PSMA-617 with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC), aiming to improve prostate-specific antigen (PSA) progression-free survival (PFS) in high-risk patients.

This phase 2 trial will enroll 160 participants and assess various outcomes, including overall survival and quality of life, while also identifying potential biomarkers to personalize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). Emmett, L., Subramaniam, S., Joshua, AM., et al.[2022]

In a study involving 40 chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC), Lutetium-177 PSMA-617 showed a best prostate-specific antigen response rate of 60%, compared to 40% for docetaxel, demonstrating its efficacy as a treatment option.

177Lu-PSMA-617 was associated with fewer severe adverse events and significantly improved quality of life compared to docetaxel, suggesting it may be a safer alternative that could be used earlier in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial. Satapathy, S., Mittal, BR., Sood, A., et al.[2022]

Lutetium-177 PSMA treatment is more likely to be effective in metastatic castration-resistant prostate cancer patients who have high baseline PSMA expression levels, particularly in bone lesions, as indicated by significant differences in SUVmax, PSMA TV, and TL PSMA values after treatment.

The study identified specific cutoff values for predicting treatment response, with a sensitivity of 91.8% for SUVmax greater than 10.50, suggesting that these parameters can help clinicians determine which patients are more likely to benefit from Lu177 PSMA therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Ga68 PSMA PET/CT imaging in Lu177 PSMA treatment planning in metastatic castration-resistant prostate cancer. Erdogan, M., Sengul, SS., Cetin, B., et al.[2022]

A case study demonstrated that 225 Ac-PSMA-617 therapy led to remission of clinical symptoms and imaging lesions in a patient with metastatic castration-resistant prostate cancer after 4 treatment cycles.

The patient experienced no observable adverse effects, suggesting that 225 Ac-PSMA-617 may be a safe and effective alternative for those who do not respond to 177 Lu-PSMA therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Multiple Bone Metastases of Castration-Resistant Prostate Cancer With 225 Ac-PSMA-617. Yang, H., Zhang, Y., Su, D., et al.[2023]

References

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

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. [2023]

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

Association between CD8 and PD-L1 expression and outcomes after radical prostatectomy for localized prostate cancer. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Prevalence and Prognostic Implications of PSA Flares during Radium-223 Treatment among Men with Metastatic Castration Resistant Prostate Cancer. [2023]

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

Sipuleucel-T for the treatment of metastatic prostate cancer: promise and challenges. [2016]

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

Antigen-Specific CD8 Lytic Phenotype Induced by Sipuleucel-T in Hormone-Sensitive or Castration-Resistant Prostate Cancer and Association with Overall Survival. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial. [2022]

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

Radium-223 dichloride: a novel treatment option for castration-resistant prostate cancer patients with symptomatic bone metastases. [2019]

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

Clinical outcomes and treatment patterns in REASSURE: planned interim analysis of a real-world observational study of radium-223 in metastatic castration-resistant prostate cancer. [2023]

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

Role of radium-223 discontinuation due to adverse events in castration-resistant prostate cancer patients. A retrospective monocentric analysis. [2023]

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

Marimastat in the treatment of patients with biochemically relapsed prostate cancer: a prospective randomized, double-blind, phase I/II trial. [2014]

11. England pubmed.ncbi.nlm.nih.gov

A Walk with Lu-177 PSMA: How Close we Have Reached from Bench to Bedside? [2021]

12. England pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial. [2022]

14. Japan pubmed.ncbi.nlm.nih.gov

The role of Ga68 PSMA PET/CT imaging in Lu177 PSMA treatment planning in metastatic castration-resistant prostate cancer. [2022]

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

Treatment of Multiple Bone Metastases of Castration-Resistant Prostate Cancer With 225 Ac-PSMA-617. [2023]