ATRA and SDK002 in Combination With Chemotherapy and Anti-PD-1 Inhibitor in Patients With Advanced Pancreatic Ductal Adenocarcinoma.

NCT07348107 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: ATARI-PDAC
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Pancreatic Ductal Adenocarcinoma

Keywords

Advanced pancreatic ductal adenocarcinoma; Metastatic; PDAC; ATRA (all-trans retinoic acid); SDK002; Tislelizumab; Gemcitabine; Nab-paclitaxel; Immune checkpoint inhibitor; Phase 1; Combination therapy; Safety and tolerability; First-line treatment; Chemotherapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as Assessed by CTCAE v5.0

  Safety will be evaluated by the incidence of adverse events (AEs), including serious adverse events (SAEs), grade 3 and 4 adverse events, adverse events of all grades, and adverse events leading to the discontinuation of study medication. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Safety outcomes will be analyzed using descriptive analyses, including the number and percentage of participants with AEs, SAEs, deaths, adverse events leading to treatment discontinuation, and adverse events by severity and relatedness. Adverse events will be summarized by system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA). Clinically significant changes in vital signs and clinical laboratory results will be summarized descriptively, and shift tables will be provided showing change in CTCAE grade from baseline to worst post-baseline grade.

  Up to 6 months.

Secondary Outcomes (1)

• 6-Month Progression-Free Survival Rate

  6 months.

Study Arms (1)

Treatment

EXPERIMENTAL

ATRA - 45mg/m2, oral, daily SDK002 - 10mg, oral, daily Gemcitabine - 800mg/m2, IV, Days 1, 8, 15 of a 28 day cycle Nab-paclitaxel - 125mg/m2, IV, Days 1, 8, 15 of a 28 day cycle Tislelizumab - 300mg, IV, Day 1 of a 28 day cycle

Drug: ATRA; Drug: Arsenic Trioxide (ATO); Drug: Gemcitabine; Drug: Nab-paclitaxel; Drug: Tislelizumab

Interventions

ATRA DRUG

Orally administered all-trans retinoic acid (ATRA) for up to 6 cycles in combination with chemotherapy and immunotherapy.

Also known as: All-Trans Retinoic Acid

Treatment

Arsenic Trioxide (ATO) DRUG

Orally administered SDK002 for up to 6 cycles in combination with chemotherapy and immunotherapy.

Also known as: SDK002

Treatment

Gemcitabine DRUG

Standard intravenous chemotherapy, administered per protocol.

Treatment

Nab-paclitaxel DRUG

Standard intravenous chemotherapy, administered per protocol.

Treatment

Tislelizumab DRUG

Anti-PD-1 immune checkpoint inhibitor, administered intravenously for up to 26 cycles.

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have previously untreated unresectable/ metastatic PDAC, without plans for a curative surgery, previous neoadjuvant therapy with 5-FU based therapy is permitted but neoadjuvant gemcitabine-based therapy must have been completed at least 6-months prior to enrollment without documented progression while on gemcitabine. Unresectable PDAC is determined based surgical assessment deeming that curative resection is not foreseeable or appropriate.
• Participants should have adequate archival tissue (from primary or metastatic tumour) available and must have provided informed consent for the release of this tissue. For potential participants who do not have adequate residual tissue or a biopsy which was only suspicious for adenocarcinoma approval from the sponsor prior to enrollment is required.
• Participants must be ≥ 18 years of age.
• Participants must have an ECOG performance status of 0 to 2.
• Participants must have a life expectancy of 3 months or longer.
• Laboratory requirements (must be done within 7 days prior to enrollment):
• Absolute neutrophils: ≥ 1.5 × 109/L (without granulocyte colony-stimulating factor support within 2 weeks prior to the first study treatment)
• Hemoglobin: ≥ 90 × 109/L
• Platelets: ≥ 100 × 109/L
• Bilirubin: \< 1.5 × ULN (Note: Exceptions may be made if confirmed diagnosis of Gilberts (\< 3 × ULN); ≤ 5.0 × ULN if participant has liver metastases or partial biliary obstruction post stenting or drainage and felt to be stable
• AST and ALT: \< 2.5 × ULN; ≤ 5.0 × ULN if participant has liver metastases or partial biliary obstruction post stenting or drainage and felt to be stable
• ALP: \< 2.5 × ULN; ≤ 5.0 × ULN if participant has liver metastases or partial biliary obstruction post stenting or drainage and felt to be stable
• Serum creatinine and creatinine clearance: ≥ 45 mL/min; (Note: Creatinine clearance to be measured directly by 24-hour urine sampling or as calculated by Cockcroft and Gault equation below:
• Females: GFR = 1.04 × \[140-age\] × weight in kg / serum creatinine in μmol/L
• Males: GFR = 1.23 × \[140-age\] × weight in kg / serum creatinine in μmol/)

You may not qualify if:

• Participants with any medical condition that would impair the administration of oral agents including significant bowel resection, inflammatory bowel disease or uncontrolled vomiting.
• Participants with a history of other malignancies, except adequately treated non-melanoma skin cancer and low-grade prostate cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \> 2 years.
• Participants may not receive concurrent treatment with other anti-cancer therapy (other than bone-targeted therapy, GnRH agonist/antagonist, or adjuvant tamoxifen and aromatase inhibitors if already taking and stable) or investigational agents while on protocol therapy. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Participants with history of allogeneic organ transplantation.
• Participants with active autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]) that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• The following autoimmune are exceptions to this criterion: 1) participants with vitiligo or alopecia; 2) participants with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; 3) participants with any chronic skin condition that does not require systemic therapy; 4) participants with celiac disease controlled by diet alone; 5) participants without an active disease in the last 5 years may be included but only after consultation with the principal investigator.
• Current or prior use of immunosuppressive medications within 14 days before first drug dose.
• The following are exceptions to this criterion: 1) intranasal, inhaled, or topical steroids or local steroid injections (e.g., intra-articular injection); 2) systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; 3) steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) or steroids a single oral dose are permitted
• History of active primary immunodeficiency.
• Participants who have received growth factors within 28 days prior to initiation of dosing of ATRA and SDK002.
• Primary prophylaxis not allowed, but secondary prophylaxis is permitted.
• Participant has known active, uncontrolled HIV, or hepatitis B or C infection.
• Participants with undetectable viral load are eligible.
• Participants with serious illnesses which would not permit the participant to be managed according to the protocol.
• Uncontrolled intercurrent illness includes but is not limited to: clinically active diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease (ILD), serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase the risk of incurring AEs, or compromise the ability of the participant to give written informed consent.

Sponsors & Collaborators

• Daniel Breadner: lead
• BeiGene (Canada) ULC: collaborator
• SDK Therapeutics, Inc.: collaborator

Study Sites (1)

Verspeeten Family Cancer Centre

London, Ontario, N6A 5W9, Canada

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Tretinoin; Arsenic Trioxide; Gemcitabine; 130-nm albumin-bound paclitaxel; tislelizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Daniel Breadner

  London Health Sciences Centre Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel Breadner

CONTACT

519-685-8600; daniel.breadner@lhsc.on.ca

Julie Mayo

CONTACT

julie.mayo@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 29, 2025
• First Posted: January 16, 2026
• Study Start: February 15, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 16, 2026

Record last verified: 2026-01

Locations

CA (1)