Study of Efficacy and Safety of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)

A Phase II, Open Label, Randomized, Parallel Arm Study of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy Gemcitabine/Nab-paclitaxel, and Gemcitabine/Nab-paclitaxel Alone in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)

The purpose of this Phase II study is to assess the efficacy and safety of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in previously untreated mPDAC.

This is a randomized, parallel arms, open-label, multi-center, Phase II study to evaluate the efficacy and safety of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel in participants with first-line metastatic pancreatic ductal adenocarcinoma (mPDAC).

The study started with a Safety Run-in to assess the safety and tolerability of NIS793 in combination with spartalizumab and standard of care (SOC) gemcitabine/nab-paclitaxel. Doses defined for each study treatment, as part of this quadruplet were administered in the Randomized part in the quadruplet/triplet/doublet-based treatment arms.

The Randomized part opened after the Safety Run-in had completed. Participants were randomized in a 1:1:1 ratio to one of the three treatment arms:

• Arm 1: NIS793 with spartalizumab and gemcitabine/nab-paclitaxel
• Arm 2: NIS793 with gemcitabine/nab-paclitaxel
• Arm 3: gemcitabine/nab-paclitaxel

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.
2. Male or female ≥ 18 years of age at the time of informed consent.
3. Participants with histologically or cytologically confirmed treatment-naïve metastatic adenocarcinoma of the pancreas with measurable disease as per RECIST 1.1.
4. Participants must have a site of disease amenable to biopsy, and be candidate for tumor biopsy according to the treating institution's guidelines. Participants must be willing to undergo a tumor biopsy at screening and during therapy on the study. In the event a new biopsy cannot be safely performed at study entry, an archival sample (collected <6 months prior) may be substituted following documented discussion with Novartis.
5. ECOG performance status ≤ 1.

Exclusion Criteria:

1. Previous radiotherapy, surgery (with exception of placement of biliary stent, which is allowed), chemotherapy or any other investigational therapy for the treatment of metastatic pancreatic cancer. Participants having received previous chemotherapy in the adjuvant setting.
2. Participants amenable to potentially curative resection.
3. Participants with a diagnosis of pancreatic neuroendocrine tumors (NETs), acinar, or islet cell tumors.
4. Having out of range laboratory values as pre-defined in the protocol.
5. Participants with MSI-H pancreatic adenocarcinoma.
6. Presence of symptomatic CNS metastases, or CNS metastases that require local CNS directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids 2 weeks prior to study entry.
7. History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
8. The participant exhibits any of the events outlined in the contra-indications or special warnings and precautions sections of gemcitabine and nab-paclitaxel as per locally approved labels.
9. Impaired cardiac function or clinically significant cardiac disease.
10. Known history of testing positive HIV infection.
11. Active HBV or HCV infection. Participants whose disease is controlled under antiviral therapy should not be excluded.
12. History of or current interstitial lung disease or pneumonitis grade ≥ 2
13. High risk of clinically significant gastrointestinal tract bleeding or any other condition associated with or history of significant bleeding.