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

Metastatic Pancreatic Ductal Adenocarcinoma Clinical Trial

— daNIS-1  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04390763
• Other study ID #: CNIS793B12201
• Secondary ID: 2020-000349-14
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 16, 2020
• Est. completion date: May 28, 2024

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 untreated mPDAC.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 164
• Est. completion date: May 28, 2024
• Est. primary completion date: May 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Ductal Adenocarcinoma

Intervention

Biological:
• NIS793
anti-TGFb antibody
• Spartalizumab
anti-PD-1 antibody

Drug:
• gemcitabine
SOC chemotherapy
• nab-paclitaxel
SOC chemotherapy

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Westmead	New South Wales
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Liege
Czechia	Novartis Investigative Site	Brno	Czech Republic
Finland	Novartis Investigative Site	Helsinki
France	Novartis Investigative Site	Paris 10
France	Novartis Investigative Site	Toulouse 4
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Ulm
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Verona	VR
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Switzerland	Novartis Investigative Site	St. Gallen
Switzerland	Novartis Investigative Site	Zurich
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
United Kingdom	Novartis Investigative Site	Oxford
United States	Winship Cancer Institute Main Centre	Atlanta	Georgia
United States	Sidney Kimmel CCC At JH	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Cente	Boston	Massachusetts
United States	Massachusetts General Hospital Massachusetts General Hospital	Boston	Massachusetts
United States	Univ of Pittsburgh Cancer Institute HIllman Cancer Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Czechia,  Finland,  France,  Germany,  Italy,  Singapore,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of DLTs during the Safety Run-in	Incidence of DLTs to assess the safety and tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel	4 weeks
Primary	Incidence and severity of treatment emergent Adverse Events and Serious Adverse Events in Safety Run-in	Safety and tolerability measured by appearance of (or worsening of any pre-existing condition) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient signed informed consent.; A Serious Adverse Event (SAE) is defined as one of the following: Is fatal or life threatening; Results in persistent or significant disability/incapacity; Constitutes a congenital anomaly/birth defect; Is medical significant; Requires inpatient hospitalization or prolongation of existing hospitalization.	8 months
Primary	Dose interruptions/reductions in Safety Run-in	Tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel measured by the number of subjects with at least one dose interruption/reduction of study treatment and reason	8 months
Primary	Dose intensity in Safety Run-in	Tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel measured by the dose intensity of study treatment for subjects with non-zero duration of exposure computed as the ratio of dose intensity and planned dose intensity	8 months
Primary	Progression-free survival in Randomized part	PFS as per Response Evaluation Criteria in Solid Tumors (RECIST1.1) as per local Investigator's review, to evaluate the PFS of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel	18 months
Secondary	Incidence and severity of Adverse Events and Serious Adverse Events in Randomized part	Safety and tolerability measured by appearance of (or worsening of any pre-existing condition) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient signed informed consent.; A Serious Adverse Event (SAE) is defined as one of the following: Is fatal or life threatening; Results in persistent or significant disability/incapacity; Constitutes a congenital anomaly/birth defect; Is medical significant; Requires inpatient hospitalization or prolongation of existing hospitalization.	18 months
Secondary	Dose interruption/reduction in Randomized part	Tolerability of NIS793 +/- spartalizumab in combination with gemcitabine/nab-paclitaxel measured by the number of subjects with at least one dose interruption/reduction of study treatment and reason	18 months
Secondary	Dose intensity in Randomized part	Tolerability of NIS793 +/- spartalizumab in combination with gemcitabine/nab-paclitaxel measured by the dose intensity of study treatment for subjects with non-zero duration of exposure computed as the ratio of dose intensity and planned dose intensity	18 months
Secondary	Overall response rate per RECIST 1.1 in Randomized part	ORR per RECIST 1.1 to assess the preliminary anti-tumor activity of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel	18 months
Secondary	Duration of response per RECIST 1.1 in Randomized part	DOR per RECIST 1.1 to assess the preliminary anti-tumor activity of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel	18 months
Secondary	Time to Progression per RECIST 1.1 in Randomized part	TTP per RECIST 1.1 to assess the preliminary anti-tumor activity of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel	18 months
Secondary	Overall Survival per RECIST 1.1 in Randomized part	OS per RECIST 1.1 to assess the preliminary anti-tumor activity of NIS793 with and without spartalizumab in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel	18 months
Secondary	CD8 and PD-L1 expression in Randomized part	Change from baseline in CD8 and PD-L1 IHC related markers to assess the CD8 and PD-L1 status of the participants at screening and on treatment versus gemcitabine/nab-paclitaxel	18 months
Secondary	Antidrug antibodies (ADA) (anti-NIS793 and anti-spartalizumab) expression in Randomized part	Antidrug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment (anti-NIS793 and anti-spartalizumab) to characterize the incidence of immunogenicity of NIS793 and spartalizumab in combination with gemcitabine/nab-paclitaxel	18 months
Secondary	Pharmacokinetic (PK) parameter Cmax in Randomized part	To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)	12 months
Secondary	Pharmacokinetic parameter AUClast in Randomized part	To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)	12 months
Secondary	Pharmacokinetic parameter Ctrough	To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)	12 months