Samuraciclib in Combination With Gemcitabine/Nab-Paclitaxel in Patients With Metastatic Basal-Like Pancreatic Cancer (SONIC)

Phase Ib/II Study of Samuraciclib in Combination With Gemcitabine/Nab-Paclitaxel in Patients With Metastatic Basal-Like Pancreatic Cancer

The purpose of this study is to find the highest dose of a drug, samuraciclib, that can be given with standard of care chemotherapy (gemcitabine and nab-paclitaxel) without causing very severe side effects. This is done by starting at a dose lower than the one that is used when samuraciclib is taken by itself without chemotherapy. The main question it aims to answer is:

• For patients with newly diagnosed metastatic pancreatic cancer, what is the safety and tolerability of samuraciclib with gemcitabine/nab-paclitaxel?

Participants will:

• Undergo a tumor biopsy.
• Be treated with samuraciclib in combination with their standard of care chemotherapy (gemcitabine/nab-paclitaxel).
• Donate research blood samples.

Study Overview

• Status: Not yet recruiting
• Conditions: Mucinous Adenocarcinoma; Pancreas Ductal Adenocarcinoma; Adenosquamous Carcinoma of the Pancreas; Pancreatic Adenocarcinoma Metastatic; Pancreas Cancer, Metastatic
• Intervention / Treatment: Drug: Samuraciclib + Gemcitabine & Nab-Paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 67
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Erica Tsang, MD; Phone Number: 4169462000; Email: Erica.Tsang@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Princess Margaret Cancer Centre
      • Contact: Anna Dodd; Phone Number: 647-539-6498; Email: Anna.Dodd@uhn.ca
      • Principal Investigator: Erica Tsang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years at the time of screening.
2. Written informed consent and any locally required authorization (eg, data privacy) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of screening.
4. Must have life expectancy ≥ 12 weeks at the time of screening.
5. Histologically or cytologically confirmed PDAC: Eligible histological variants include: mucinous adenocarcinoma, independent cell adenocarcinoma, adenosquamous carcinoma, adenocarcinoma not otherwise specified (NOS).
6. Dose Escalation: All patients with metastatic PDAC will be permitted to enrol.
7. Dose Expansion: Patients with metastatic basal-like PDAC will be permitted to enrol, based on the PurIST assay or by transcriptomic sequencing. Patients will be permitted to start no more than one cycle of gemcitabine/nab-paclitaxel while waiting for transcriptional subtype results in the dose expansion cohort.
8. Radiographic evidence of metastatic disease that is measurable per RECIST 1.1.
9. Adequate organ and marrow function within 28 days prior to dosing on Day 1.
10. Adequate liver function (AST ≤2.5 times the institutional upper limit of normal, total bilirubin ≤2 times the institutional upper limit of normal) at the baseline visit. Patients are permitted to enroll with biliary obstruction, as long as they undergo appropriate biliary decompression (can be done at the same time as endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB)) and hepatic parameters have improved at time of baseline visit.
11. Patients must have either de novo metastatic disease or recurrence >6 months after completion of neoadjuvant or adjuvant intent systemic therapy.
12. Patients must have recovered to ≤ Grade 1 in terms of toxicity from prior treatments at the time of enrollment (excluding neuropathy which can be ≤ Grade 2, and alopecia)
13. Patients must be able to take oral medications.
14. Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from screening to 180 days after the final dose of study treatment. It is strongly recommended for the male partner of a female patient to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
15. Nonsterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom with spermicide from screening to 180 days after receipt of the final dose of study treatment. It is strongly recommended for the female partner of a male patient to also use a highly effective method of contraception throughout this period. In addition, male patients must refrain from sperm donation while on study and for 180 days after the final dose of study treatment.

Exclusion Criteria:

1. Participants receiving any other study agents concurrently with the study drugs.
2. Known homologous recombination deficient pancreatic cancer, including germline or somatic BRCA1/2 or PALB2 mutations
3. Concurrent enrolment in another therapeutic clinical study. Enrolment in observational or supportive care studies will be allowed.
4. History of a malabsorption syndrome or uncontrolled nausea, vomiting, or diarrhea that may interfere with the absorption of oral study medication in the opinion of the investigator.
5. Patients with a history of Grade 3 or greater thromboembolic events in the prior 3 months to the scheduled first dose of study treatment or thromboembolic event of any grade with ongoing symptoms.
6. Patients with prior history of myocardial infarction, transient ischemic attack, congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification or stroke within the past 3 months prior to the scheduled first dose of study treatment.
7. Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
8. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
9. Other invasive malignancy within 2 years. Non-invasive malignancies (ie, cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, ductal carcinoma in situ of the breast that has been surgically cured) are excluded from this definition. Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of study treatment and of low potential risk for recurrence are permitted.
10. Known allergy or hypersensitivity to investigational product formulations.
11. Active grade 3 or greater edema (eg, peripheral, pulmonary).
12. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
13. Participants with known untreated brain metastases are excluded. Patients with a history of brain metastases are permitted to enroll if they have been treated and have been stable for a minimum of one month on imaging. Participants must be off all corticosteroids at the time of enrolment.
14. Major surgery (as defined by the investigator) within 28 days prior to scheduled first dose of study treatment or still recovering from prior surgery. Local procedures (eg, placement of a systemic port, core needle biopsy, etc) are allowed, without needing to wait for the 28 day recovery period.
15. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study.
16. Any condition that, in the opinion of the investigator, would interfere with safe administration or evaluation of the investigational products or interpretation of patient safety or study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Samuraciclib + GnP; Samuraciclib + Standard of Care Chemotherapy (Gemcitabine & Nab-Paclitaxel)	Drug: Samuraciclib + Gemcitabine & Nab-Paclitaxel; Starting dose level: Samuraciclib 240 mg taken orally, once daily. Gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8 and 15.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequencies of adverse events (AEs), as graded by CTCAE v6.0 and reported by dose level		From date of enrollment to date off treatment, assessed up to 24 months
Percentages of adverse events (AEs), as graded by CTCAE v6.0 and reported by dose level		From date of enrollment to date off treatment, assessed up to 24 months
Frequencies of dose-limiting toxicities reported by dose level		From date of enrollment to date off treatment, assessed up to 24 months
Percentages of dose-limiting toxicities reported by dose level		From date of enrollment to date off treatment, assessed up to 24 months
Maximum tolerated dose, defined as the highest dose level where a dose-limiting toxicity occurs within at most one out of six patients treated		From date of enrollment to date off treatment, assessed up to 24 months
Recommended phase II dose (RP2D)	The RP2D will be selected based on the evaluation of dose-limiting toxicities and adverse events measured using CTCAE v6.0.	From date of enrollment to date off treatment, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Defined as the proportion of participants who achieve a Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 best overall response of confirmed complete response (CR) or confirmed partial response (PR)	From date of enrollment to date off treatment, assessed up to 24 months
Progression-free survival (PFS)	Defined as the duration of time from start of treatment to time of disease recurrence/progression (PD) or death from any cause, whichever occurs first.	From date of enrollment to date of first progression or death, assessed up to 24 months
Overall survival (OS)	Defined as the duration of time from time of diagnosis to death.	From date of enrollment to date of death, assessed up to 24 months
Duration of overall response (DOR)	Defined as the duration of time from when measurement criteria are met for CR or PR (whichever is first recorded) until the date that recurrent/progressive disease (PD) is objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started).	From date of enrollment to date of first progression, assessed up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of PDAC transcriptional subtype (basal vs classical) between baseline and 8 week sample	Evaluate translational biomarkers related to CDK7 inhibition with samuraciclib by comparing tissue and blood samples at pre-treatment and at 8 weeks.	From enrollment to 8 weeks on treatment

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: June 18, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Neoplastic Processes; Carcinoma; Neoplasms, Cystic, Mucinous, and Serous; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Pancreatic Neoplasms; Adenocarcinoma, Mucinous; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: OZUHN-049

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes