Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06624644
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-27
Brief Title:
A Trial of LNS8801 with or Without Pembrolizumab in Patients with Refractory Melanoma
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Multicenter Open-Label Randomized Controlled Study to Assess the Antitumor Activity of LNS8801 with and Without Pembrolizumab in Patients with Treatment-Refractory Unresectable Melanoma
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this clinical trial is to understand if a new drug called LNS8801 can safely treat patients with melanoma The primary question to be answered is what is the average length of time during which melanoma does not grow or spread after starting treatment with LNS8801 Researchers will compare LNS8801 taken alone or LNS8801 taken together with another drug called pembrolizumab to other therapies as decided by the treating doctor
135 patients will be randomly like flipping a coin placed in 3 treatment groups
In the first group LNS8801 only - Patients will take 125mg tablet of LNS8801 by mouth once per day every day for up to 2 years
In the second group LNS8801 pembrolizumab - Patients will take 125mg tablet of LNS8801 by mouth once per day plus 200 mg of pembrolizumab by IV infusion once every 3 weeks for up to 2 years
In the third group called Physicians Choice PC patients will receive chemotherapy dacarbazine or temozolomide or immunotherapy pembrolizumab nivolumabrelatlimab or nivolumabipilimumab as determined by their treating physician
How often the patient visits the clinic visits will depend on the treatment group Besides returning to the clinic for treatment the patient will undergo periodic safety assessments and other required study procedures such as imaging assessments
135 patients will be randomly like flipping a coin placed in 3 treatment groups
In the first group LNS8801 only - Patients will take 125mg tablet of LNS8801 by mouth once per day every day for up to 2 years
In the second group LNS8801 pembrolizumab - Patients will take 125mg tablet of LNS8801 by mouth once per day plus 200 mg of pembrolizumab by IV infusion once every 3 weeks for up to 2 years
In the third group called Physicians Choice PC patients will receive chemotherapy dacarbazine or temozolomide or immunotherapy pembrolizumab nivolumabrelatlimab or nivolumabipilimumab as determined by their treating physician
How often the patient visits the clinic visits will depend on the treatment group Besides returning to the clinic for treatment the patient will undergo periodic safety assessments and other required study procedures such as imaging assessments
Detailed Description:
This is a randomized controlled open-label multicenter study to characterize the safety tolerability and antitumor effects of LNS8801 alone and in combination with pembrolizumab in treatment refractory unresectable cutaneous melanoma patients who are homozygous for the consensus GPER protein-coding amino acid sequence CC and have progressed on prior immune checkpoint inhibitor therapy including an anti-PD-1 therapy The CC form of GPER is present in approximately 55 of patients
Patients must initially consent to a prescreening blood-based genetic test only Patients with the required genotype will then consent to full screening and treatment and the potential physicians choice PC treatment will be identified Patients will be randomized 111 between LNS8801 pembrolizumab LNS8801 monotherapy and PC treatment In the LNS8801 pembrolizumab arm LNS8801 will be administered every day per week and pembrolizumab will be administered 200 mg Q3W for up to 35 cycles approximately 2 years Note Physicians may modify the pembrolizumab regimen to 400 mg Q6W pembrolizumab after 6 months of treatment if appropriate In the monotherapy arm LNS8801 will be administered every day per week In the PC arm patients may receive chemotherapy dacarbazine temozolomide or immunotherapy pembrolizumab nivolumabrelatlimab nivolumabipilimumab
Patients randomization will be stratified by normal or elevated baseline LDH 3 or 3 disease sites and physicians determination of primary vs secondary anti-PD-1 therapy resistance per SITC guidelines prior to randomization the preferred PC treatment for each patient will be identified and the patient must be willing to receive this therapy if assigned to the PC arm At least one-third of patients in each arm must have had secondary resistance to prior anti-PD-1 therapy Patients who are on LNS8801 pembrolizumab combination therapy may drop one of the study medications and continue on the other for tolerability or safety reasons For example if a patient has an immune-related AE that warrants discontinuation of pembrolizumab they should continue LNS8801 monotherapy Patients may choose to remain on study drugs past progression if they are clinically stable and the treating physician believes that continued therapy is likely to benefit the patient
Patients may continue on LNS8801 therapy past progression and initiate localized therapy if they are clinically stable and the treating physician believes that continued LNS8801 therapy is likely to benefit the patient Safety assessments will be performed on all patients at screening throughout their participation in the study and at either 30 days following the last dose of study drugs if they are not taking an immune checkpoint inhibitor ICI or 90 days following the last dose if their treatment included an ICI Measures of metabolic health eg circulating lipids blood pressure HbA1C will also be recorded throughout the study
Overall survival and reason for mortality should be assessed after the last dose of study medication every 6 months for the first year and then annually until it has been 2 years since any patient has taken study medication Any anti-cancer therapies should be recorded
Imaging of tumors for evidence of tumor response andor progression will be performed at screening within 21 days of the first dose of study drug and then every 8 weeks for the first year every 12 weeks for the second year and every 6 months thereafter
Up to 135 patients will be randomized in this study
Patients must initially consent to a prescreening blood-based genetic test only Patients with the required genotype will then consent to full screening and treatment and the potential physicians choice PC treatment will be identified Patients will be randomized 111 between LNS8801 pembrolizumab LNS8801 monotherapy and PC treatment In the LNS8801 pembrolizumab arm LNS8801 will be administered every day per week and pembrolizumab will be administered 200 mg Q3W for up to 35 cycles approximately 2 years Note Physicians may modify the pembrolizumab regimen to 400 mg Q6W pembrolizumab after 6 months of treatment if appropriate In the monotherapy arm LNS8801 will be administered every day per week In the PC arm patients may receive chemotherapy dacarbazine temozolomide or immunotherapy pembrolizumab nivolumabrelatlimab nivolumabipilimumab
Patients randomization will be stratified by normal or elevated baseline LDH 3 or 3 disease sites and physicians determination of primary vs secondary anti-PD-1 therapy resistance per SITC guidelines prior to randomization the preferred PC treatment for each patient will be identified and the patient must be willing to receive this therapy if assigned to the PC arm At least one-third of patients in each arm must have had secondary resistance to prior anti-PD-1 therapy Patients who are on LNS8801 pembrolizumab combination therapy may drop one of the study medications and continue on the other for tolerability or safety reasons For example if a patient has an immune-related AE that warrants discontinuation of pembrolizumab they should continue LNS8801 monotherapy Patients may choose to remain on study drugs past progression if they are clinically stable and the treating physician believes that continued therapy is likely to benefit the patient
Patients may continue on LNS8801 therapy past progression and initiate localized therapy if they are clinically stable and the treating physician believes that continued LNS8801 therapy is likely to benefit the patient Safety assessments will be performed on all patients at screening throughout their participation in the study and at either 30 days following the last dose of study drugs if they are not taking an immune checkpoint inhibitor ICI or 90 days following the last dose if their treatment included an ICI Measures of metabolic health eg circulating lipids blood pressure HbA1C will also be recorded throughout the study
Overall survival and reason for mortality should be assessed after the last dose of study medication every 6 months for the first year and then annually until it has been 2 years since any patient has taken study medication Any anti-cancer therapies should be recorded
Imaging of tumors for evidence of tumor response andor progression will be performed at screening within 21 days of the first dose of study drug and then every 8 weeks for the first year every 12 weeks for the second year and every 6 months thereafter
Up to 135 patients will be randomized in this study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None