LAVA-1207 for Prostate Cancer

No longer recruiting at 14 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Male

Trial Phase: Phase 1

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LAVA-1207 for men with prostate cancer that has spread and does not respond to standard hormone therapy. Researchers aim to assess the safety and effectiveness of LAVA-1207, both alone and in combination with other drugs like interleukin-2 or Pembrolizumab. This treatment may suit men who have tried chemotherapy and hormone treatments without success and whose cancer continues to progress. Participants should be able to identify if they have prostate cancer that has spread and not responded to past treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

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

Research has shown that LAVA-1207 was well tolerated in early studies. The safety data indicate it performed as expected, with no safety issues halting its development; it was stopped for other reasons, such as not meeting certain goals.

When combined with Pembrolizumab or low-dose IL-2, studies have not identified any safety concerns. Early results from these combinations align with researchers' expectations, with no unexpected or severe side effects reported.

In summary, LAVA-1207 and its combinations have been well tolerated so far, based on early study data. However, as this is the first time it is being tested in humans, ongoing research will continue to closely monitor its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for prostate cancer, which often include hormone therapy, chemotherapy, or radiation, LAVA-1207 offers a new approach by targeting specific proteins on cancer cells. Researchers are excited about LAVA-1207 because it leverages a bispecific antibody that directs the body's immune cells to attack the cancer, potentially leading to more precise and effective results. Additionally, when combined with pembrolizumab or low-dose IL-2, LAVA-1207 might enhance the immune response even further. This novel mechanism could offer a promising alternative for patients who have limited options with existing therapies.

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

Research shows that LAVA-1207 is designed to activate certain immune cells to attack cancer cells. In early studies, this drug helped destroy prostate cancer cells. In this trial, some participants will receive LAVA-1207 alone, while others will receive it with Pembrolizumab, which has been safe and has shown early signs of shrinking tumors in patients who no longer respond to standard treatments. Another group in this trial will receive LAVA-1207 with a low dose of interleukin-2 (IL-2) to enhance the immune response. Although these results are promising, more research is needed to confirm its effectiveness in people. ^{2 4 6 7 8}

Who Is on the Research Team?

Clinical Trials Management

Principal Investigator

Lava Therapeutics

Are You a Good Fit for This Trial?

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

I have tried and not responded to a taxane-based chemotherapy before.

Exclusion Criteria

Known clinically relevant immunodeficiency disorders.

I do not have any ongoing or uncontrolled infections.

My heart condition is unstable.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2672

Phase I/II trial of LAVA-1207, a novel bispecific gamma- ... Preclinical evidence demonstrates that, upon binding both targets, LAVA-1207 leads to potent Vγ9Vδ2-T cell degranulation and cytolytic activity ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05369000

Trial of LAVA-1207 in Patients With Therapy Refractory ... This is a phase 1, first-in-human study to evaluate Safety, Tolerability, PK, PD, Immunogenicity, and Antitumor Activity of LAVA-1207 alone or with low dose ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT395058

Early dose escalation of LAVA-1207, a novel bispecific ... Methods: This is an open label, 3+3 design, phase 1/2a study in patients with therapy refractory metastatic castration resistant prostate cancer (NCT05369000; ...

4. withpower.com withpower.com/trial/lava-1207-for-prostate-cancer-5ed32

LAVA-1207 for Prostate Cancer · Info for Participants The available research does not provide specific data on the effectiveness of LAVA-1207 for prostate cancer. Instead, it discusses other treatments like ...

5. ir.lavatherapeutics.com ir.lavatherapeutics.com/news-releases/news-release-details/lava-therapeutics-announces-treatment-first-patient-phase-12a-0

News Release - Investor Relations - LAVA Therapeutics N.V. Based on the compelling preclinical data of LAVA-1207 in prostate cancer, we believe our Gammabody™ platform has the potential to provide ...

6. onclive.com onclive.com/view/development-of-lava-1207-discontinues-in-mcrpc

Development of LAVA-1207 Discontinues in mCRPC LAVA-1207 development was discontinued due to unmet internal benchmarks, not safety concerns, in a phase 1/2a trial for PSMA-positive mCRPC.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.153

Early dose escalation of LAVA-1207, a novel bispecific ... Conclusions: LAVA-1207 has been well tolerated early in dose escalation; further clinical activity including PSA results, response assessment, ...

8. lavatherapeutics.com lavatherapeutics.com/wp-content/uploads/2023/02/LAVA-1207_2023-ASCO-GU-poster_final_30Jan2023.pdf

Early dose escalation of LAVA-1207, a novel bispecific ... LAVA-1207 administered via IV infusion every 2 weeks. • Objectives: investigate safety and tolerability, evaluate PK, PD, immunogenicity and preliminary ...