Clinical trial NCT06108050: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Metastatic Solid Tumor
Keywords: Advanced Solid Tumor
Metastatic Solid Tumor
JZP898
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2023-10-30
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria

* Adult ≥ 18 years of age
* Histological or cytological diagnosis of advanced or metastatic solid tumor.

  1. Previously treated participants with solid tumors (eg. 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.
  2. Parts A2 and B: previously-treated (≥ 1 line of prior anticancer therapy) participants with select tumor types (NSCLC, HNSCC, melanomas, RCC, and UC) who have progressed on/after prior CPI therapy based on investigator assessment per RECIST version 1.1.
* 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 version 1.1 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 (noninfectious) or interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* 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 or have had a history of radiation pneumonitis
* 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

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicities in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Incidence of TEAEs and SAEs in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Incidence of dose interruptions, discontinuation, and reductions due to TEAEs in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Objective Response Rate (ORR) As Assessed by the Investigator In Combination Therapy
timeFrame: Up to 36 months
Secondary outcomes:
measure: Pharmacokinetic Parameter: Maximum Concentration (Cmax) of JZP898 in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Pharmacokinetic Parameter: Time to Maximum Concentration (Tmax) of JZP898 in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Pharmacokinetic Parameter: Terminal Elimination Half-life (t½) of JZP898 in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of JZP898 in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Pharmacokinetic Parameter: Clearance (CL) of JZP898 in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Pharmacokinetic Parameter: Volume of Distribution (V) of JZP898 in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Pharmacokinetic Parameter: Activated IFNα-to-JZP898 Ratio in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Pharmacokinetic Parameter: Accumulation ratio for Cmax in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: Pharmacokinetic Parameter: Accumulation Ratio for AUC in Monotherapy and Combination Therapy
timeFrame: Up to 36 months
measure: ORR As Assessed by the Investigator in Monotherapy
timeFrame: Up to 36 months
measure: Duration of Response (DoR) As Assessed by the Investigator
timeFrame: Up to 36 months
measure: Disease Control Rate (DCR) As Assessed by the Investigator
timeFrame: Up to 36 months
measure: Progression-free Survival (PFS) As Assessed by the Investigator
timeFrame: Up to 36 months
measure: Overall Survival (OS)
timeFrame: Up to 36 months
measure: Incidence of ADAs towards JZP898
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: Fresno
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Durham
country: United States
facility: Duke University Medical Center - Duke Cancer Institute
state: North Carolina
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
References: