Study of Efficacy and Safety of NIS793 in Combination With Standard of Care (SOC) Chemotherapy in First-line Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2

Official Title

A Randomized, Double-blind, Phase III Study, Comparing NIS793 in Combination With Gemcitabine and Nab-paclitaxel Versus (vs.) Placebo Combined With Gemcitabine and Nab-paclitaxel for First Line Treatment of Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - daNIS-2

Summary:

The purpose of this study is to evaluate the efficacy and safety of NIS793 in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel and placebo in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC). This study aims to explore whether blockade of Transforming Growth Factor β (TGFβ) in combination with gemcitabine/nab-paclitaxel can reduce fibrosis in PDAC, restore chemo-sensitivity and ultimately lead to improvements in overall survival (OS) and other clinically relevant outcomes.

Trial Description

Primary Outcome:

  • Safety run-in part: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment.
  • Randomized part: Overall survival (OS)
Secondary Outcome:
  • Percentage of participants with Adverse Events (AEs)
  • Percentage of participants with dose interruptions and dose reductions of NIS793 in combination with gemcitabine and nab-paclitaxel
  • Dose intensity of NIS793 in combination with gemcitabine and nab-paclitaxel
  • Progression-free survival (PFS) by investigator assessment per RECIST 1.1
  • Overall response rate (ORR) by investigator assessment per RECIST 1.1
  • Disease control rate (DCR) by investigator assessment per RECIST 1.1
  • Time to response (TTR) by investigator assessment per RECIST 1.1
  • Safety run-in part: Overall Survival (OS)
  • Maximum concentration (Cmax) of NIS793 in combination with gemcitabine and nab-paclitaxel
  • Trough Concentration (Ctrough) of NIS793 in combination with gemcitabine and nab-paclitaxel
  • Area under the curve from time zero to the last measurable concentration sampling time (AUClast) of NIS793 in combination with gemcitabine and nab-paclitaxel
  • Area under the curve calculated to the end of a dosing interval (tau) at steady-state (AUCtau) of NIS793 in combination with gemcitabine and nab-paclitaxel
  • Time to reach maximum concentration (Tmax) of NIS793 in combination with gemcitabine and nab-paclitaxel
  • Randomized part: NIS793 serum concentration
  • Randomized part: Change from baseline in the patient reported outcomes measurement information system (PROMIS)-29 profile scores at week 12
  • Randomized part: Change from baseline in the European Quality of life questionnaire (EQ-5D-5L) scores (health index and EQ-VAS) at week 12
  • Randomized part: Time-to-deterioration in domain scores in the PROMIS-29 profile
  • Randomized part: Time-to-deterioration in EQ-5D-5L scores (health index and EQ-VAS)
  • Randomized part: Anti-drug antibodies (ADA) against NIS793 prevalence at baseline
  • Randomized part: ADA (anti-NIS793) incidence on treatment

This is a randomized, double-blind, multicenter two-arm, phase III study that has two parts:

  • Safety run-in part: An open-label safety run-in part will be conducted to confirm recommended phase 3 dose (RP3D) of NIS793 in combination with gemcitabine and nab-paclitaxel. Up to approximately 10 participants will be enrolled at each dose level to achieve at least 6 evaluable participants; however, if the starting dose is not recommended and a lower dose level is tested, 10 additional participants will be enrolled. The decision to open the randomized part will be based on dose confirmation and available safety, relevant PK, and other relevant data from run-in part
  • Randomized part: Enrolled participants will be randomized to the two treatment arms.

The study treatment will be administered as a 28-day treatment cycle. Participants will be treated until unacceptable toxicity, disease progression per RECIST 1.1, withdrawal of consent or any other condition of treatment discontinuation specified in the protocol.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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