JZP898 Intravenous Infusion as Monotherapy and Combination With Pembrolizumab in Adults With Advanced/Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT06108050
• Recruitment Status: Recruiting
• First Posted: October 30, 2023
• Last Update Posted: April 19, 2024
• Sponsor: Jazz Pharmaceuticals
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Jazz Pharmaceuticals

Tracking Information

• First Submitted Date: October 19, 2023
• First Posted Date: October 30, 2023
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: November 7, 2023
• Estimated Primary Completion Date: November 30, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 26, 2023)

• Number of Participants with Dose Limiting Toxicities [ Time Frame: Up to 36 months ]
• Incidence of TEAEs and SAEs [ Time Frame: Up to 36 months ]
• Incidence of dose interruptions, discontinuation, and reductions due to TEAEs [ Time Frame: Up to 36 months ]
• Objective Response Rate (ORR) As Assessed by the Investigator [ Time Frame: Up to 36 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 26, 2023)

• Pharmacokinetic Parameter: Maximum Concentration (Cmax) of JZP898 [ Time Frame: Up to 36 months ]
• Pharmacokinetic Parameter: Time to Maximum Concentration (Tmax) of JZP898 [ Time Frame: Up to 36 months ]
• Pharmacokinetic Parameter: Terminal Elimination Half-life (t½) of JZP898 [ Time Frame: Up to 36 months ]
• Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of JZP898 [ Time Frame: Up to 36 months ]
• Pharmacokinetic Parameter: Clearance (CL) of JZP898 [ Time Frame: Up to 36 months ]
• Pharmacokinetic Parameter: Volume of Distribution (V) of JZP898 [ Time Frame: Up to 36 months ]
• Pharmacokinetic Parameter: Activated IFNα-to-JZP898 Ratio [ Time Frame: Up to 36 months ]
• Mean Dose Proportionality of JZP898 and Activated IFNα [ Time Frame: Up to 36 months ]
• Pharmacokinetic Parameter: Accumulation ratio for Cmax [ Time Frame: Up to 36 months ]
• Pharmacokinetic Parameter: Accumulation Ratio for AUC [ Time Frame: Up to 36 months ]
• Mean JZP898 and Activated IFNα Concentrations [ Time Frame: Up to 36 months ]
• ORR As Assessed by the Investigator [ Time Frame: Up to 36 months ]
• Duration of Response (DoR) As Assessed by the Investigator [ Time Frame: Up to 36 months ]
• Disease Control Rate (DCR) As Assessed by the Investigator [ Time Frame: Up to 36 months ]
• Progression-free Survival (PFS) As Assessed by the Investigator [ Time Frame: Up to 36 months ]
• Overall Survival (OS) [ Time Frame: Up to 36 months ]
• Incidence of ADAs towards JZP898 [ Time Frame: Up to 36 months ]
• Changes in tumor immune cell profile in response to monotherapy and combination therapy as measured by gene expression (nanoString) [ Time Frame: Up to 36 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: JZP898 Intravenous Infusion as Monotherapy and Combination With Pembrolizumab in Adults With Advanced/Metastatic Solid Tumors
• Official Title: A Phase 1, First-in-human, Open-label, Multicenter Study of JZP898 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors
• Brief Summary: This Phase 1 first-in-human study will investigate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of JZP898 monotherapy as well as JZP898 in combination with pembrolizumab in adult participants with advanced or metastatic solid tumors.

Detailed Description

Two-part study: Part A Dose Exploration (Parts A1 and A2) and Part B Combination Expansion.

Part A Dose Exploration:

• Part A1 - a monotherapy dose exploration to determine the monotherapy recommended dose and/or maximum tolerated dose (MTD) and safety profile of JZP898.
• Part A2 - a combination dose exploration of JZP898 plus pembrolizumab to determine the combination recommended dose followed by confirmation of the recommended phase 2 dose (Combination RP2D)

Part B Combination Expansion:

• Part B - combination expansion using a basket design to evaluate clinical antitumor activity and safety profile of JZP898 in combination with pembrolizumab at the Combination RP2D identified in Part A2.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Solid Tumor
• Metastatic Solid Tumor

Intervention

• Drug: JZP898
  Investigational drug monotherapy
• Drug: Pembrolizumab
  Approved anti-PD1 antibody
  Other Name: KEYTRUDA®

Study Arms

• Experimental: Part A1 Dose Exploration: JZP898 monotherapy
  Intervention: Drug: JZP898
• Experimental: Part A2 Dose Exploration: JZP898 in combination with pembrolizumab
  Interventions:

  • Drug: JZP898
  • Drug: Pembrolizumab
• Experimental: Part B Combination Expansion: JZP898 in combination with pembrolizumab
  Interventions:

  • Drug: JZP898
  • Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 26, 2023): 177
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2028
• Estimated Primary Completion Date: November 30, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

• Adult ≥ 18 years of age

• Histological or cytological diagnosis of advanced or metastatic solid tumor.

  a. Previously treated participants with solid tumors (NSCLC, melanoma, HNSCC, RCC, HCC, gastroesophageal carcinomas, UC, or CRC [MSI-H]) for whom, in the opinion of the investigator, there is no SoC available to convey clinical benefit.

• Participants in select tumor types:

  1. NSCLC: eligible for platinum-based therapy and received platinum-based therapy prior to inclusion in the study.
  2. HNSCC: eligible for platinum therapy and received platinum-based therapy prior to inclusion in this study.
  3. Melanoma with known BRAFv600 mutation: received BRAF/MEKi therapy before this study.
• ECOG score of 0 to 1.
• Measurable disease per RECIST v1.1 criteria.
• Parts A1 and A2 only: willing to consent to mandatory tumor biopsies (both pretreatment and post-treatment with JZP898) unless medically infeasible
• Adequate organ and bone marrow function as indicated by the following laboratory values (within 4 weeks prior to starting the study interventions)
• Men and women of reproductive potential to observe highly effective birth control for the duration of treatment and for 4 months following the last dose of study drug;
• Additional criteria may apply

Exclusion Criteria

• Unresolved toxicities > Grade 1.
• Hypersensitivity to mAb, IFNα, or study intervention components.
• Primary CNS tumor or symptomatic CNS metastases.
• Have a second primary malignancy treated within the previous 2 years (exceptions: non-metastatic, non-melanomatous skin cancers, carcinoma in-situ, and melanoma in-situ).
• Active autoimmune disease (in the last 2 years) requiring systemic steroids or immunosuppressive agents.
• Active or history of pneumonitis or interstitial lung disease requiring steroid treatment.
• Any history of suicidal behavior or any suicidal ideation
• Clinically significant ischemic/hemorrhagic cerebrovascular accident/stroke and/or clinically significant active cardiovascular disease
• Received any anticancer therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug
• Received prior radiotherapy within 2 weeks of the first dose of study drug
• Major surgery within 2 weeks prior to the first dose of study intervention.
• Participant is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study
• Had an allogeneic tissue/solid organ transplant.
• Receipt of prior IFNα therapy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trial Disclosure & Transparency; 215-832-3750; ClinicalTrialDisclosure@JazzPharma.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06108050
• Other Study ID Numbers: JZP898-101; KEYNOTE-F62 ( Other Identifier: Merck Sharp & Dohme LLC ); MK-3475-F62 ( Other Identifier: Merck Sharp & Dohme LLC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jazz Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Jazz Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Not Provided
• PRS Account: Jazz Pharmaceuticals
• Verification Date: April 2024