Breakthrough Clinical Results
Plus Therapeutics announced the treatment of the first patients in its ReSPECT-LM dose optimization trial for REYOBIQ™ (rhenium Re186 obisbemeda) in leptomeningeal metastases (LM). This trial follows promising Phase 1 results showing REYOBIQ's feasibility in treating LM. The study, aligned with the FDA's Project Optimus, aims to determine the optimal dose for maximum efficacy and safety. Rapid enrollment is anticipated due to the significant unmet need for LM treatments. Plus Therapeutics plans to present data at the SNO/ASCO CNS Metastases Conference and request an End of Phase 1 meeting with the FDA to discuss the next steps in clinical development.
Key Highlights
- Initial patients treated in ReSPECT-LM dose optimization trial for REYOBIQ™ in leptomeningeal metastases (LM).
- Trial builds on promising Phase 1 results demonstrating REYOBIQ's feasibility in treating LM.
- Study designed to optimize dosing for maximum efficacy and safety, aligned with FDA's Project Optimus.
- Rapid trial enrollment expected due to significant unmet medical need.
Incidence and Prevalence
Global Epidemiology of Leptomeningeal Metastases
Incidence and Prevalence
Leptomeningeal metastases occur in approximately 5% of patients with solid tumors, although autopsy findings reveal these lesions much more frequently in 10-20% of cases. The incidence of LM is increasing due to advances in neuroimaging, poor central nervous system penetration of drugs, and prolonged overall survival of patients.
In comparison, brain metastases are more common, seen in 20%-50% of patients with metastatic solid tumors, while leptomeningeal disease (LMD) occurs more rarely.
The incidence of leptomeningeal metastases has gradually increased over time, and continues to rise annually, emphasizing the urgent need for early recognition and treatment initiation.
Distribution Across Cancer Types
Leptomeningeal metastases (LM) are most commonly observed in hematological malignancies. The incidence of non-Hodgkin's lymphoma has been increasing in recent decades. In one study of non-Hodgkin's lymphoma with leptomeningeal metastases, diffuse large B cell lymphoma was the most common cancer subtype (21/27, 78%). More than half of the patients with non-Hodgkin's lymphoma and leptomeningeal metastases showed extranodal involvement (18/27, 67%).
Among solid tumors, the most frequent primary sites are lung and breast cancers, two tumors where the incidence of LMM is apparently increasing. With prolonged survival in solid tumors, an increased frequency of metastases is noted in these tumors too.
Specifically, breast cancer, lung cancer and melanoma metastasize to the meninges in 5-15% of patients. Leptomeningeal metastasis is a fatal complication of breast cancer which results when cancer cells seed in the meninges.
Prognosis and Survival
The prognosis for patients with leptomeningeal metastases is poor. Currently there is no cure, limiting survival to less than four months. Despite recent developments in cancer therapy, survival of these patients is usually less than six months.
The overall prognosis remains grim and quality of life should remain the priority when deciding which treatment option to apply. Patients with leptomeningeal metastases have short survival durations and poor quality of life.
Associated Complications
In one study, 70% of patients with neoplastic meningitis (19 out of 27) had evidence of cerebrospinal fluid flow disturbances, which can further complicate treatment and prognosis.
Mechanism of Action
Mechanisms of Action in Trials for Leptomeningeal Metastases
Based on the provided context, there is no specific information available about the mechanisms of action in trials for drugs that have not been approved for leptomeningeal metastases. The context indicates that after reviewing all input strings, no specific information was found about trials for drugs targeting leptomeningeal metastases or their mechanisms of action.
The context mentions that while there was information about various cancer treatments, drug resistance mechanisms, and clinical trials for different conditions, none specifically addressed leptomeningeal metastases.
Therefore, I cannot provide details about the three most common mechanisms of action, molecular mechanisms of action in clinical trials for investigational agents, or pharmacological target pathways being investigated for leptomeningeal metastases or leptomeningeal carcinomatosis.
Drug used in other indications
REYOBIQ™ Clinical Trials Beyond Leptomeningeal Metastases
After carefully reviewing all available information, I cannot provide details about other indications for which REYOBIQ™ (rhenium Re186 obisbemeda) is being trialed beyond leptomeningeal metastases. The provided context does not contain specific information about:
- Additional clinical indications for REYOBIQ™
- Active clinical trials investigating rhenium Re186 obisbemeda for other conditions
- Intervention models, dosing regimens, or treatment protocols for REYOBIQ™ in any indication
- Specific treatment paradigms being utilized in clinical trials
The available information does not mention REYOBIQ™ or rhenium Re186 obisbemeda in relation to any clinical indications or trials.