daNIS-1: Study of Efficacy and Safety of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04390763
• Collaborator: (none)
• Enrollment: 161
• Locations: 31
• Arms: 4
• Anticipated Duration (Months): 36.2
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Ductal Adenocarcinoma	Biological: NIS793; Biological: Spartalizumab; Drug: gemcitabine; Drug: nab-paclitaxel	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 161 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Oct 16, 2020
• Anticipated Primary Completion Date: Oct 24, 2023
• Anticipated Study Completion Date: Oct 24, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Safety Run-in Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel	Biological: NIS793; anti-TGFb antibody; Biological: Spartalizumab; anti-PD-1 antibody; Other Names: PDR001 ; Drug: gemcitabine; SOC chemotherapy; Drug: nab-paclitaxel; SOC chemotherapy; Other Names: abraxane
Experimental: Randomized Arm 1 Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel	Biological: NIS793; anti-TGFb antibody; Biological: Spartalizumab; anti-PD-1 antibody; Other Names: PDR001 ; Drug: gemcitabine; SOC chemotherapy; Drug: nab-paclitaxel; SOC chemotherapy; Other Names: abraxane
Experimental: Randomized Arm 2 Combination of NIS793 + gemcitabine + nab-paclitaxel	Biological: NIS793; anti-TGFb antibody; Drug: gemcitabine; SOC chemotherapy; Drug: nab-paclitaxel; SOC chemotherapy; Other Names: abraxane
Active Comparator: Randomized Arm 3 gemcitabine + nab-paclitaxel	Drug: gemcitabine; SOC chemotherapy; Drug: nab-paclitaxel; SOC chemotherapy; Other Names: abraxane

Outcome Measures

Primary Outcome Measures

1. Incidence of DLTs during the Safety Run-in [8 months]

   Incidence of DLTs to assess the safety and tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel

2. Incidence and severity of treatment emergent Adverse Events and Serious Adverse Events in Safety Run-in [8 months]

   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.

3. Dose interruptions/reductions in Safety Run-in [8 months]

   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

4. Dose intensity in Safety Run-in [8 months]

   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

5. Progression-free survival in Randomized part [18 months]

   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

Secondary Outcome Measures

1. Incidence and severity of Adverse Events and Serious Adverse Events in Randomized part [18 months]

   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.

2. Overall response rate per RECIST 1.1 in Randomized part [18 months]

   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

3. Duration of response per RECIST 1.1 in Randomized part [18 months]

   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

4. Time to Progression per RECIST 1.1 in Randomized part [18 months]

   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

5. Overall Survival per RECIST 1.1 in Randomized part [18 months]

   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

6. CD8 and PD-L1 expression in Randomized part [18 months]

   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

7. Antidrug antibodies (ADA) (anti-NIS793 and anti-spartalizumab) expression in Randomized part [18 months]

   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

8. Pharmacokinetic (PK) parameter Cmax in Randomized part [12 months]

   To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)

9. Pharmacokinetic parameter AUClast in Randomized part [12 months]

   To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)

10. Pharmacokinetic parameter Ctrough [12 months]

    To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University School of Medicine/Winship Cancer Institute	Atlanta	Georgia	United States	30322
2	Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Med	Baltimore	Maryland	United States	21231
3	Massachusetts General Hospital Massachusetts General Hospital	Boston	Massachusetts	United States	02114
4	Beth Israel Deaconess Medical Cente	Boston	Massachusetts	United States	02215
5	University of Pittsburgh Cancer Institute HIllman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
6	Novartis Investigative Site	Westmead	New South Wales	Australia	2145
7	Novartis Investigative Site	Melbourne	Victoria	Australia	3000
8	Novartis Investigative Site	Salzburg		Austria	5020
9	Novartis Investigative Site	Wien		Austria	A-1090
10	Novartis Investigative Site	Liege		Belgium	4000
11	Novartis Investigative Site	Brno	Czech Republic	Czechia	656 53
12	Novartis Investigative Site	HUS		Finland	FIN-00029
13	Novartis Investigative Site	Paris Cedex 10		France	75475
14	Novartis Investigative Site	Toulouse Cedex 4		France	31054
15	Novartis Investigative Site	Essen		Germany	45147
16	Novartis Investigative Site	Heidelberg		Germany	69120
17	Novartis Investigative Site	Ulm		Germany	89081
18	Novartis Investigative Site	Milano	MI	Italy	20132
19	Novartis Investigative Site	Milano	MI	Italy	20141
20	Novartis Investigative Site	Rozzano	MI	Italy	20089
21	Novartis Investigative Site	Verona	VR	Italy	37126
22	Novartis Investigative Site	Singapore		Singapore	119074
23	Novartis Investigative Site	Singapore		Singapore	169610
24	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
25	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
26	Novartis Investigative Site	Madrid		Spain	28050
27	Novartis Investigative Site	St. Gallen		Switzerland	9007
28	Novartis Investigative Site	Zurich		Switzerland	8091
29	Novartis Investigative Site	Taichung		Taiwan	40447
30	Novartis Investigative Site	Taipei		Taiwan	10002
31	Novartis Investigative Site	Oxford		United Kingdom	OX3 7LJ

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04390763
• Other Study ID Numbers: CNIS793B12201; 2020-000349-14
• First Posted: May 18, 2020
• Last Update Posted: Apr 20, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: NIS793, spartalizumab, gemcitabine, nab-paclitaxel, mPDAC, TGFβ, PD-1, Phase II
• Additional relevant MeSH terms: Adenocarcinoma; Gemcitabine; Paclitaxel; Spartalizumab

Study Results

No Results Posted as of Apr 20, 2022