E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pancreatic ductal adenocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033604 |
E.1.2 | Term | Pancreatic cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Safety Run-in part:
• To assess the safety and tolerability of NIS793 with spartalizumab in combination with gemcitabine/nab-paclitaxel.
Randomized part:
• To evaluate the Progression Free Survival (PFS) per Investigator assessment of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus SOC chemotherapy gemcitabine/nab-paclitaxel.
• To evaluate the PFS of NIS793 with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
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E.2.2 | Secondary objectives of the trial |
Randomized part:
• To evaluate the safety and tolerability of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
• To assess the preliminary anti-tumor activity of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
• To assess Overall Survival (OS) of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel
• To assess the CD8 and PD-L1 status of the participants at screening and on treatment versus gemcitabine/nab-paclitaxel
• To characterize the incidence of immunogenicity of NIS793 and spartalizumab in combination with gemcitabine/nab-paclitaxel
• To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants with histologically or cytologically confirmed treatment naïve metastatic adenocarcinoma of the pancreas with measurable disease per RECIST 1.1.
Participants must have a site of disease amenable to biopsy, be candidate for tumor biopsy, and must be willing to undergo a tumor biopsy at screening and during therapy on the study.
ECOG performance status ≤ 1 |
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E.4 | Principal exclusion criteria |
Previous radiotherapy, surgery (note: placement of biliary stent is allowed), chemotherapy or investigational therapy for the treatment of metastatic disease. Participants having received previous chemotherapy in the adjuvant setting
Participants with MSI-H pancreatic adenocarcinoma
Participants with a diagnosis of pancreatic neuroendocrine tumors (NETs), acinar, or islet cell tumors
Participants amenable to potentially curative resection
Presence of symptomatic CNS metastases or CNS metastases that require local CNS-directed therapy
History of severe hypersensitivity reactions to other monoclonal antibodies
Malignant disease other than that being treated in the study
Systemic chronic steroid therapy (>10mg/day prednisone or equivalent) or any immunosuppressive therapy
Known history of testing positive for HIV infection
Active HBV and HCV infection
Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment
Active, known or suspected autoimmune disease
History of or current pneumonitis or interstitial lung disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety Run-in part:
1) Incidence of DLTs during the first 4 weeks of treatment
2) Safety: Incidence and severity of treatment emergent AEs and SAEs, changes between baseline and post-baseline laboratory parameters, vital signs, and ECG parameters
3) Tolerability: Dose interruptions, reductions and dose intensity
Randomized part:
4) Progression-free survival based on Response Evaluation Criteria in Solid Tumors (RECIST1.1) as per local Investigator’s review |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) DLT observation period 4 weeks
2), 3), 4) end of study |
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E.5.2 | Secondary end point(s) |
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and ECGs, dose interruptions, reductions, and dose intensity
Overall response rate (ORR), Duration of response (DOR), Time to Progression (TTP) RECIST 1.1 as per local Investigator’s review
Overall Survival (OS)
Change from baseline in CD8 and PD-L1 IHC related markers
Antidrug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment (anti-NIS793 and anti-spartalizumab)
Pharmacokinetic parameters (e.g. Ctrough, Cmax, AUClast)
PK concentration time profiles
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
as per protocol Table 8-1 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Singapore |
Switzerland |
Taiwan |
Australia |
Austria |
Belgium |
Canada |
Czechia |
Finland |
France |
Germany |
Italy |
Japan |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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• All participants have discontinued study treatment and completed the safety follow-up and at least 80% of the participants have died, withdrawn consent or are lost to follow-up.
• Another study becomes available that can continue to provide participants’ study treatment, and all participants ongoing are transferred to that clinical study and all discontinued participants have completed the safety follow-up period.
• The study is terminated early. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 19 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |