Molecularly Tailored Therapy Versus Standard Care in Advanced Pancreatic Cancer with Actionable Molecular Alterations

Primary objective: to compare the efficacy of molecularly tailored therapy versus standard of care in advanced pancreatic cancer with actionable reimbursed druggable molecular alterations, as assessed by progression-free survival. This endpoint is clinically relevant because it evaluates disease control over time. Secondary objectives: to compare overall survival, including median overall survival and overall survival rates at 6 and 12 months; to assess antitumor activity by objective response rate, disease control rate, and duration of response; to compare safety and tolerability; and to assess quality of life.

The sponsor did not provide the total number of participants. The trial population included adult patients with advanced pancreatic cancer, and both female and male participants were represented. The age range was not specified in the source, although eligibility was limited to adults aged 18 years and over. Participants were selected from patients with pancreatic cancer confirmed by cytology or histology, with available personalized molecular testing results and treatment options, and with disease progression during or after one line of systemic chemotherapy in the advanced setting or within one year of adjuvant or neoadjuvant treatment. The population also required an ECOG Performance Status of 0 to 2 and normal organ and marrow function. Relevant lifestyle-related requirements included contraceptive use for women of childbearing potential and for sexually active men with women of childbearing potential. No information was provided on diet, physical activity, or other habits.

The study is a phase II trial in advanced pancreatic cancer designed to compare molecularly tailored therapy with standard of care. The trial uses an unspecified comparative design based on the available data, with treatment assigned to a test regimen or a comparator regimen according to the protocol. Study procedures begin with a screening visit to confirm eligibility, including informed consent, review of prior treatment, performance status, organ and marrow function, and availability of a personalized molecular report. After enrollment, participants undergo treatment and scheduled follow-up visits for assessment of efficacy, safety, and patient-reported outcomes. The end-of-study visit is performed at treatment completion or study discontinuation to document final clinical status and outcomes. The overall trial duration is estimated from 2026-10-01 to 2032-06-30, and participant involvement is expected to continue until disease progression, completion of protocol-defined assessments, or early termination. Early termination may occur for progression, unacceptable toxicity, withdrawal of consent, non-compliance, or other protocol-specified reasons.

The trial evaluated molecularly tailored therapy versus standard care in advanced pancreatic cancer. The experimental treatments included olaparib, erlotinib, crizotinib, trametinib, pemigatinib, selpercatinib, axitinib, vismodegib, pembrolizumab, larotrectinib, dabrafenib, and trastuzumab/pertuzumab as Phesgo. These agents were administered by the oral route at doses of 600 mg, 150 mg, 500 mg, 2 mg, 13.5 mg, 320 mg, 20 mg, 150 mg, 200 mg, 200 mg, and 300 mg, respectively. Phesgo was administered by subcutaneous injection as a solution for injection at a dose of 1 dosage form, with two strengths used: 600 mg/600 mg and 1200 mg/600 mg.

The comparator treatments were capecitabine, oxaliplatin, irinotecan, fluorouracil, calcium folinate, gemcitabine, and paclitaxel albumin-bound. Capecitabine was given orally at 1650 mg/m2, oxaliplatin intravenously at 130 mg/m2, irinotecan intravenously at 200 mg/m2, fluorouracil by intravenous infusion at 2400 mg/m2, calcium folinate intravenously at 400 mg/m2, gemcitabine intravenously at 1000 mg/m2, and paclitaxel albumin-bound intravenously at 125 mg/m2. No additional information on dosing schedules or participant compliance monitoring was specified.

Efficacy will be assessed by progression-free survival as the primary endpoint. Secondary efficacy assessments will include overall survival, overall survival rates at 6 and 12 months, objective response rate, disease control rate, duration of response, and progression-free survival on subsequent treatment (PFS 2). Adjusted mean change from baseline in global health status/QoL score, and functional and symptom scales from the EORTC QLQ-C30 questionnaire will also be evaluated.