ATRA and SDK002 in Combination With Chemotherapy and Anti-PD-1 Inhibitor in Patients With Advanced Pancreatic Ductal Adenocarcinoma.
brief summary
This study is testing whether adding three drugs, All-Trans Retinoic Acid (ATRA), SDK002 (also called Arsenic Trioxide or ATO), and tislelizumab, to standard chemotherapy is safe for people with advanced pancreatic cancer. Advanced pancreatic cancer means the cancer has spread or cannot be removed with surgery. The study will also look at whether this treatment combination may help people live longer. Participants will receive standard chemotherapy drugs, gemcitabine and nab-paclitaxel, together with ATRA, SDK002, and tislelizumab. ATRA is related to vitamin A and may affect how cancer cells grow. SDK002 is a drug used to treat sine cancers and may help other treatments work better. Tislelizumab is an immunotherapy drug, which helps the immune system recognize and attack cancer cells. This is a phase 1 study, which means the main goal is to test safety and side effects. All participants receive the same treatment, and both the study doctors and participants know which drugs are being given.
detailed description
This is a Phase 1, open-label, single center study to evaluate the safety of ATRA and SDK002 when given with gemcitabine, nab-paclitaxel and tislelizumab in participants with previously untreated, unresectable/metastatic pancreatic ductal adenocarcinoma. The enrolment target is 6 to 10 participants over 6 months.
An initial safety run-in will cap the gemcitabine dose at 800 mg/m2 in addition to standard dose ATRA, SDK002, nab-paclitaxel and tislelizumab. If the first 3 participants receiving 800 mg/m2 gemcitabine at each C1 administration do not experience grade 3+ AEs related to gemcitabine, the Steering Committee (SC) will review the data and may approve the option to escalate gemcitabine to the standard maximum dose of 1000 mg/m2 at C2D1 for subsequent participants. Safety data for participants treated at 1000 mg/m2 will be reviewed at each applicable SC meeting. Once a safe dose has been established, accrual will halt and the SC will establish the maximum dose of gemcitabine permitted in a future Phase 2 study.
After a screening period of up to 28 days, each participant will receive orally administered ATRA and SDK002 for a maximum of 6 cycles in combination with gemcitabine and nab-paclitaxel (until progression or unacceptable toxicity), and tislelizumab (for a maximum of 2 years or until progression or unacceptable toxicity). After treatment, each participant will be followed for 2 years, or until recurrence/death is documented, whichever comes first.
Participants may continue both ATRA and SDK002 while on at least one chemotherapy agent (gemcitabine or nab-paclitaxel) and/or immune checkpoint inhibitor (tislelizumab). Participants who permanently discontinue both the immune checkpoint inhibitor and the entire chemotherapy regimen must stop ATRA and SDK002, at which point the participant will be considered off protocol treatment.
All participants are highly recommended to have fresh tumor biopsies collected between C2 and C3. If a participant withdraws consent for this biopsy they will not be removed from the study, but should only be accrued if their initial intent is to undergo an on treatment biopsy.
Participants will return for a Safety Follow-up Visit 28 (± 7) days after the end of the last cycle. Participants who experience disease progression/relapse will enter Survival Follow-up and be contacted every 3 months after the end of the last cycle date for late onset immune related AEs, then every 6 months until death.
Safety will be assessed by AEs, clinical laboratory evaluation (serum chemistry, hematology, coagulation, and urinalysis), physical examination, vital signs measurements, ECGs (including QTc interval), and ECOG performance status.
official title
A Phase 1 Study of ATRA and SDK002 in Combination With Chemotherapy and Anti-PD-L1 Inhibitor in Patients With Advanced Pancreatic Ductal Adenocarcinoma.