Study of Efficacy and Safety of NIS793 (With and Without Spartalizumab) in Combination With SOC Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC)
- Conditions
- Metastatic Pancreatic Ductal Adenocarcinoma
- Interventions
- Registration Number
- NCT04390763
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed 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 & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 164
- Signed informed consent must be obtained prior to participation in the study.
- Male or female ≥ 18 years of age at the time of informed consent.
- Participants with histologically or cytologically confirmed treatment-naïve metastatic adenocarcinoma of the pancreas with measurable disease as per RECIST 1.1.
- 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.
- ECOG performance status ≤ 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.
- Participants amenable to potentially curative resection.
- Participants with a diagnosis of pancreatic neuroendocrine tumors (NETs), acinar, or islet cell tumors.
- Having out of range laboratory values as pre-defined in the protocol.
- Participants with MSI-H pancreatic adenocarcinoma.
- 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.
- History of severe hypersensitivity reactions to any ingredient of study drug(s) and other mAbs and/or their excipients.
- 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.
- Impaired cardiac function or clinically significant cardiac disease.
- Known history of testing positive HIV infection.
- Active HBV or HCV infection. Participants whose disease is controlled under antiviral therapy should not be excluded.
- History of or current interstitial lung disease or pneumonitis grade ≥ 2
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Safety Run-in NIS793 Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel Safety Run-in gemcitabine Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel Safety Run-in Spartalizumab Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel Randomized Arm 1 NIS793 Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel Safety Run-in nab-paclitaxel Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel Randomized Arm 1 Spartalizumab Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel Randomized Arm 1 nab-paclitaxel Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel Randomized Arm 3 nab-paclitaxel gemcitabine + nab-paclitaxel Randomized Arm 2 NIS793 Combination of NIS793 + gemcitabine + nab-paclitaxel Randomized Arm 2 nab-paclitaxel Combination of NIS793 + gemcitabine + nab-paclitaxel Randomized Arm 2 gemcitabine Combination of NIS793 + gemcitabine + nab-paclitaxel Randomized Arm 1 gemcitabine Combination of NIS793 + spartalizumab + gemcitabine + nab-paclitaxel Randomized Arm 3 gemcitabine gemcitabine + nab-paclitaxel
- Primary Outcome Measures
Name Time Method 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.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
Incidence of DLTs during the Safety Run-in 4 weeks Incidence of DLTs to assess the safety and tolerability of NIS793 + spartalizumab in combination with gemcitabine/nab-paclitaxel
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
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
Name Time Method 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
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
Pharmacokinetic parameter Ctrough 12 months To characterize the pharmacokinetics (PK) of NIS793, spartalizumab, gemcitabine/nab-paclitaxel in combination treatment or alone (gemcitabine/nab-paclitaxel)
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.Dose intensity in Randomized part 18 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
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
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
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
Dose interruption/reduction in Randomized part 18 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
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
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)
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)
Trial Locations
- Locations (6)
Beth Israel Deaconess Medical Cente
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Novartis Investigative Site
🇬🇧Oxford, United Kingdom
Univ of Pittsburgh Cancer Institute HIllman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Winship Cancer Institute Main Centre
🇺🇸Atlanta, Georgia, United States
Sidney Kimmel CCC At JH
🇺🇸Baltimore, Maryland, United States