Description:
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.
Title
- Brief Title: Study of Efficacy and Safety of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)
- 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 IDs
- ORG STUDY ID:
CNIS793B12201
- SECONDARY ID:
2020-000349-14
- NCT ID:
NCT04390763
Conditions
- Metastatic Pancreatic Ductal Adenocarcinoma
Interventions
Drug | Synonyms | Arms |
---|
NIS793 | | Randomized Arm 1 |
Spartalizumab | PDR001 | Randomized Arm 1 |
gemcitabine | | Randomized Arm 1 |
nab-paclitaxel | abraxane | Randomized Arm 1 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Safety Run-in | Experimental | Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel | - NIS793
- Spartalizumab
- gemcitabine
- nab-paclitaxel
|
Randomized Arm 1 | Experimental | Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel | - NIS793
- Spartalizumab
- gemcitabine
- nab-paclitaxel
|
Randomized Arm 2 | Experimental | Combination of NIS793 + gemcitabine + nab-paclitaxel | - NIS793
- gemcitabine
- nab-paclitaxel
|
Randomized Arm 3 | Active Comparator | gemcitabine + nab-paclitaxel | - gemcitabine
- nab-paclitaxel
|
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of DLTs during the Safety Run-in |
Time Frame: | 8 months |
Safety Issue: | |
Description: | Incidence of DLTs to assess the safety and tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel |
Secondary Outcome Measures
Measure: | Incidence and severity of Adverse Events and Serious Adverse Events in Randomized part |
Time Frame: | 18 months |
Safety Issue: | |
Description: | 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. |
Measure: | Overall response rate per RECIST 1.1 in Randomized part |
Time Frame: | 18 months |
Safety Issue: | |
Description: | 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 |
Measure: | Duration of response per RECIST 1.1 in Randomized part |
Time Frame: | 18 months |
Safety Issue: | |
Description: | 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 |
Measure: | Time to Progression per RECIST 1.1 in Randomized part |
Time Frame: | 18 months |
Safety Issue: | |
Description: | 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 |
Measure: | Overall Survival per RECIST 1.1 in Randomized part |
Time Frame: | 18 months |
Safety Issue: | |
Description: | 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 |
Measure: | CD8 and PD-L1 expression in Randomized part |
Time Frame: | 18 months |
Safety Issue: | |
Description: | 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 |
Measure: | Antidrug antibodies (ADA) (anti-NIS793 and anti-spartalizumab) expression in Randomized part |
Time Frame: | 18 months |
Safety Issue: | |
Description: | 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 |
Measure: | Pharmacokinetic (PK) parameter Cmax in Randomized part |
Time Frame: | 12 months |
Safety Issue: | |
Description: | To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel) |
Measure: | Pharmacokinetic parameter AUClast in Randomized part |
Time Frame: | 12 months |
Safety Issue: | |
Description: | To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel) |
Measure: | Pharmacokinetic parameter Ctrough |
Time Frame: | 12 months |
Safety Issue: | |
Description: | To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel) |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- NIS793, spartalizumab, gemcitabine, nab-paclitaxel, mPDAC, TGFβ, PD-1, Phase II
Last Updated
July 21, 2021