Metastatic pancreatic ductal adenocarcinoma Cancer
Conditions
Interventions
Current interventions as of 13/07/2026:
Module 1: Participants will receive ginisortamab (investigational medicinal product [IMP]) administered by 30 (+10)-minute intravenous (IV) infusion once every
however, those participants deemed to be benefiting from ginisortamab in combination with cobimetinib, who are not experiencing any severe adverse reactions, may be considered for treatment beyond 12
Sponsors
Cancer Research UK
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 13/07/2026: Applicable to All Trial Participants: 1. Written (signed and dated) informed consent, and capable of co-operating with IMP/s (and SoC [auxiliary medicinal products], as applicable) administration and follow-up. 2. Histologically or cytologically confirmed diagnosis of PDAC with metastatic disease. 3. Consent for pre- and on-treatment tumour biopsy samples for assessment of molecular markers, including but not limited to SMAD4 and gremlin-1. Pre- and on-treatment tumour samples are mandatory in the first instance. These tumour samples may become optional as considered appropriate by the Sponsor and Investigators based on a review of emerging data during the trial. Participants must have disease amenable to biopsy as deemed safe by the Investigator. 4. Measurable disease according to RECIST Version 1.1. 5. Eastern Cooperative Oncology Group performance status of =1. 6. Haematological and biochemical indices within defined ranges. These measurements should be performed to confirm the patient's eligibility to participate in the trial. 7. Aged 18 years or over at the time consent is given. Module 2 – Additional Inclusion Criteria: 1. Investigator determination that the clinical interests of the participant are best served by stopping SoC induction therapy (FOLFIRINOX, or nab-paclitaxel plus gemcitabine) after attainment of a best response of = SD. 2. At least ongoing SD or response (CR/PR) after =16 weeks of treatment with a SoC first-line induction regimen (FOLFIRINOX, or nab-paclitaxel plus gemcitabine). - Ongoing SD or response must be confirmed on the trial baseline scan. 3. Not a candidate for PARP inhibitor maintenance therapy. Previous inclusion criteria as of 07/04/2026: Applicable to All Trial Participants: 1. Written (signed and dated) informed consent, and capable of co-operating with IMP (and SoC) administration and follow-up. 2. Histologically or cytologically confirmed diagnosis of PDAC with metastatic disease. 3. Consent for pre- and on-treatment tumour biopsy samples for assessment of molecular markers, including but not limited to, SMAD4 and gremlin-1. Pre- and on-treatment tumour samples are mandatory in the first instance. These tumour samples may become optional as considered appropriate by the Sponsor and Investigators based on a review of emerging data during the trial. Participants must have disease amenable to biopsy as deemed safe by the Investigator. 4. Measurable disease according to RECIST Version 1.1. 5. Eastern Cooperative Oncology Group performance status of =1. 6. Haematological and biochemical indices within defined ranges. These measurements should be performed to confirm the patient's eligibility to participate in the trial. 7. Aged 18 years or over at the time consent is given. Module 2 – Additional Inclusion Criteria: 1. Investigator determination that the clinical interests of the participant are best served by stopping SoC induction therapy (FOLFIRINOX, or nab-paclitaxel plus gemcitabine) after attainment of a best response of = SD. 2. At least ongoing SD or response (CR/PR) after =16 weeks of treatment with a SoC first-line induction regimen (FOLFIRINOX, or nab-paclitaxel plus gemcitabine). - Ongoing SD or response must be confirmed on the trial baseline scan. 3. Not a candidate for PARP inhibitor maintenance therapy. Original inclusion criteria: Module 1: 1. Written (signed and dated) informed consent, and capable of co-operating with IMP (and SoC) ad
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 13/07/2026: Applicable to All Trial Participants: 1. Prior radiotherapy to the only measurable index lesion unless radiological progression has occurred following completion of radiotherapy. 2. Radiotherapy (for non-metastatic disease) within the last 6 months prior to Cycle 1 Day 1 with the exception of palliative treatment (=10 Gy single fraction or 25 Gy fractionated total) that has been completed at least 7 days prior to Cycle 1 Day 1. 3. Previous investigational therapy for the treatment of metastatic PDAC. 4. Previous concurrent anti-cancer treatment within 28 days or 5 half-lives (whichever is shorter) prior to Cycle 1 Day 1 (e.g. cytoreductive therapy, immunotherapy, biologic therapy, or cytokine therapy [with the exception of erythropoietin]). 5. Live vaccinations will not be permitted within 28 days before trial enrolment or randomisation. 6. Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma. 7. Prior neo-adjuvant, peri-operative, or adjuvant chemotherapy for non-metastatic pancreatic adenocarcinoma with curative intent unless recurrent (i.e. metastatic) disease is documented more than 6 months since the last dose of systemic therapy. Exception applies. 8. Clinically significant/symptomatic third space fluid accumulation (e.g. ascites or pleural effusion). 9. Ongoing toxic manifestations of previous treatments considered by the Investigator to make the patient unsuitable for the trial. 10. Brain or leptomeningeal metastases. 11. Clinically significant ongoing pulmonary disease, including but not limited to interstitial lung disease, idiopathic pulmonary fibrosis or pulmonary hypersensitivity pneumonitis. 12. History of pulmonary embolism or deep vein thrombosis unless continuing anticoagulant treatment as clinically indicated. 13. Major thoracic or abdominal surgery from which the patient has not yet recovered. 14. At high medical risk because of non-malignant systemic disease, including active uncontrolled infection. Patients with previous hepatitis C virus (HCV) exposure but no current infection are eligible to participate. Any uncontrolled active systemic infection requiring systemic IV treatment that was completed =7 days before Cycle 1 Day 1. 15. Known to be serologically positive for hepatitis B virus (HBV), HCV or HIV. Patients who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have an undetectable HCV RNA by polymerase chain reaction (PCR) or HBV DNA (by PCR) that is 450 ms measured on triplicate ECG (if an average QTcF of >450 ms then the patient is ineligible). 19. Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase II trial of ginisortamab. Participation in an observational trial or interventional clinical trial that does not involve administration of an IMP, and that would not place an unacceptable burden on the patient, in the opinion of the Investigator, would be acceptable. 20. Current or prior malignancy that could affect safety or efficacy assessment of the IMP or compliance with the protocol or interpretation of r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcomes as of 13/07/2026: Module 1: 1. Frequency of adverse events (AEs) considered at least possibly related to ginisortamab, and the number of Grade 3, 4 and 5 AEs at least possibly related to ginisortamab for up to an initial maximum of 12 cycles (~1 year) and no more than 24 cycles (~2 years). AEs, including relatedness, seriousness and severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, will be assessed by the Investigator. Evaluation of this endpoint will occur once the last participant enrolled to Module 1 has received up to 24 cycles (~2 years) of ginisortamab. 2. Recommended dose of ginisortamab for use with standard of care (SoC) nab-paclitaxel and ginisortamab following the review of all available clinically relevant data, including but not limited to toxicity, efficacy and PK data by the Sponsor and Investigators. Evaluation of this endpoint will occur once all participants in the module have completed the safety run-in period (28 days) and all relevant data have been collected. 3. Progression-free survival (PFS), defined as the time from the date of starting ginisortamab plus SoC nab-paclitaxel and gemcitabine to the date of disease progression or date of death, whichever occurs first. Response will be assessed at baseline, at the end of every 8 weeks and at end of treatment. Participants who withdraw from the trial due to reasons other than progression will be followed up for survival for up to 12 months after the date upon which the last participant enrolled to Module 1 receives their first dose of ginisortamab. 4. Disease control rate (DCR), defined as the proportion of participants who achieve a best response of complete response (CR), partial response (PR), or stable disease (SD) of duration =16 weeks, evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1. Response will be assessed at baseline, at the end of every 8 weeks and at | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcomes as of 13/07/2026: Module 1: 1. Overall survival (OS), calculated from the date of starting ginisortamab plus SoC nab-paclitaxel and gemcitabine to the date of death. Participant status will be reviewed throughout the trial and for up to 12 months after the date upon which the last participant enrolled to Module 1 receives their first dose of ginisortamab. 2. Overall response rate (ORR), defined as the proportion of participants who achieve a best response of CR or PR according to RECIST Version 1.1. Response will be assessed at baseline, at the end of every 8 weeks and at end of treatment. 3. Duration of response (DoR), defined as the time from the date of the first confirmed CR or PR according to RECIST Version 1.1 to the date of disease progression. Response will be assessed at baseline, at the end of every 8 weeks and at end of treatment. Participants who withdraw from the trial due to reasons other than progression will be followed up for survival for up to 12 months after the date upon which the last participant enrolled to Module 1 receives their first dose of ginisortamab. 4. Time to next therapy (TTNT), defined as the time from the date of starting ginisortamab plus SoC nab-paclitaxel and gemcitabine to the date of starting the next treatment regimen following discontinuation of trial treatment in this trial. Participant status will be reviewed throughout the trial and for up to 12 months after the date upon which the last participant enrolled to Module 1 receives their first dose of ginisortamab. 5. PK parameters for ginisortamab when given with SoC nab-paclitaxel and gemcitabine, including maximum observed plasma concentration (Cmax), area under the concentration-time curve (AUC), terminal elimination half-life (T1/2), volume of distribution at steady state (Vss), clearance (CL) and trough concentration (Ctrough) for the safety run-in, and Cmax and Ctrough for the dose expansion. Samples for PK analysis will be taken at up to 17 | — |
Countries
England, Germany, Northern Ireland, Norway, Scotland, Spain, United Kingdom, Wales
Contacts
Public ContactJosephine;Olivia Salimu;Frank
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Outcome results
None listed