Phase II, open label, randomized multicenter study to evaluate efficacy and safety of study treatment in previously untreated patients with advanced pancreatic cancer. Patients will receive study treatment for a maximum of 24 months or until progression disease or until unacceptable toxicity. In the experimental arm, patients who discontinue chemotherapy for reasons other than disease progression may continue receiving the remaining study drugs (NLM-001, botensilimab and balstilimab) up to a maximum of 24 months, according to schedule.
Participants will be centrally randomized 1:1 to one of the study arms. Randomization will be stratified according to: 1. ECOG Performance Status (0 vs 1) 2. Presence of liver metastases (yes vs no)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Gemcitabine 1,000 mg / m2 IV administered on days 1, 8 and 15 in cycles of 28 days.
Nab-P 125 mg / m2 IV administered on days 1, 8 and 15 in cycles of 28 days.
NLM-001: 800 mg/day, p.o, once daily (4 tablets of 200 mg) days -4 to -1 and 10-13 of each cycle.
Botensilimab: 75 mg every 6 weeks for 4 administrations, from D1C1.
Balstilimab: 240 mg IV Day 1 and Day 15 of each 28-day cycle.
Hospital Universitario Miguel Servet
Zaragoza, Aragon, Spain
Hospital Clínic Barcelona
Barcelona, Barcelona, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, Spain
Hospital Universitario de Donostia
San Sebastián, Gipuzkoa, Spain
Complexo Hospitalario Universitario de Santiago
Santiago de Compostela, La Coruña, Spain
Hospital Universitario Virgen de la Victoria
Málaga, Málaga, Spain
To evaluate the response rate in each of the study arms, assessed according to iRECIST criteria, including the confirmation of progression to distinguish true progression from potential pseudoprogression.
Objective Response Rate (ORR): Complete Response (CR) + Partial Response (PR), according to iRECIST 1.1 criteria, according to investigator criteria. Suspected progression (including possible pseudoprogression due to immune-related effects or new lesions) must be confirmed with repeat imaging performed 4-8 weeks after the initial assessment before considering the patient as having true disease progression.
Time frame: 12 months
To evaluate safety profile and tolerability of study treatment according to NCI-CTCAE v 5.0 criteria.
Safety profile will be assessed according to NCI-CTCAE v 5.0 criteria. The number of patients experiencing each AE will be summarized by CTCAE grade.
Time frame: 12 months
To evaluate treatment efficacy according to progression free survival (PFS)
Progression Free Survival (PFS): PFS is defined as the time in months from the patient's randomization until patient progression according to iRECIST 1.1 criteria or death.
Time frame: 12 months
To evaluate treatment efficacy according to 6 months PFS
Progression Free Survival (PFS): PFS is defined as the time in months from the patient's randomization until patient progression according to iRECIST 1.1 criteria or death.
Time frame: 6 months
To evaluate treatment efficacy according todisease control rate (DCR)
Disease Control Rate (DCR): Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) evaluated by iRECIST 1.1 criteria according to investigator criteria.
Time frame: 12 months
To evaluate treatment efficacy according to duration of response (DoR)
Duration of Response (DoR): DoR is defined as the time in months from the date of first documented objective response (complete response \[CR\] or partial response \[PR\], whichever is first) until the date of first documented disease progression or death from any cause, whichever occurs first.
Time frame: 12 months
To evaluate treatment efficacy according to duration of clinical benefit (DoCB)
Duration of Clinical Benefit (DoCB): DoCB is defined, for subjects achieving clinical benefit (complete response \[CR\], partial response \[PR\], or stable disease \[SD\] per iRECIST v1.1), as the time from the date of first documented evidence of clinical benefit (CR, PR, or SD) until the date of first documented radiographic disease progression or death from any cause, whichever occurs first.
Time frame: 12 months
To evaluate treatment efficacy according to overall survival.
Overall Survival (OS): OS is defined as the time in months from the patient's randomization until death.
Time frame: 12 months
To evaluate CA 19.9 levels during study treatment (Decrease > 50%)
Decrease in CA 19.9 levels \> 50%. Responses based on levels of the tumor marker CA 19.9 will be calculated as the maximum percentage of change with respect to baseline in those patients with a baseline higher than 1.25 times the upper limit of normal in the local laboratory of each center.
Time frame: 12 months
To evaluate CA 19.9 levels during study treatment (Decrease > 75%)
Decrease in CA 19.9 levels \> 75%. Responses based on levels of the tumor marker CA 19.9 will be calculated as the maximum percentage of change with respect to baseline in those patients with a baseline higher than 1.25 times the upper limit of normal in the local laboratory of each center.
Time frame: 12 months
To evaluate CA 19.9 levels during study treatment (Decrease > 90%).
Decrease in CA 19.9 levels \> 90%. Responses based on levels of the tumor marker CA 19.9 will be calculated as the maximum percentage of change with respect to baseline in those patients with a baseline higher than 1.25 times the upper limit of normal in the local laboratory of each center.
Time frame: 12 months
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