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

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06108050
• Other study ID #: JZP898-101
• Secondary ID: KEYNOTE-F62MK-34
• Status: Recruiting
• Phase: Phase 1
• Start date: November 7, 2023
• Est. completion date: May 31, 2028

Study information

• Verified date: April 2024
• Source: Jazz Pharmaceuticals
• Contact: Clinical Trial Disclosure & Transparency
• Phone: 215-832-3750
• Email: ClinicalTrialDisclosure[@]JazzPharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 177
• Est. completion date: May 31, 2028
• Est. primary completion date: November 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, IFNa, 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 IFNa therapy

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Metastatic Solid Tumor
• Neoplasms

Intervention

Drug:
• JZP898
Investigational drug monotherapy
• Pembrolizumab
Approved anti-PD1 antibody

Locations

Country	Name	City	State
United States	Texas Oncology - Baylor Charles A Sammons Cancer Center	Dallas	Texas
United States	Duke University Medical Center - Duke Cancer Institute	Durham	North Carolina
United States	California Cancer Associates for Research and Excellence	Encinitas	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	California Cancer Associates for Research and Excellence	Fresno	California
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose Limiting Toxicities		Up to 36 months
Primary	Incidence of TEAEs and SAEs		Up to 36 months
Primary	Incidence of dose interruptions, discontinuation, and reductions due to TEAEs		Up to 36 months
Primary	Objective Response Rate (ORR) As Assessed by the Investigator		Up to 36 months
Secondary	Pharmacokinetic Parameter: Maximum Concentration (Cmax) of JZP898		Up to 36 months
Secondary	Pharmacokinetic Parameter: Time to Maximum Concentration (Tmax) of JZP898		Up to 36 months
Secondary	Pharmacokinetic Parameter: Terminal Elimination Half-life (t½) of JZP898		Up to 36 months
Secondary	Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of JZP898		Up to 36 months
Secondary	Pharmacokinetic Parameter: Clearance (CL) of JZP898		Up to 36 months
Secondary	Pharmacokinetic Parameter: Volume of Distribution (V) of JZP898		Up to 36 months
Secondary	Pharmacokinetic Parameter: Activated IFNa-to-JZP898 Ratio		Up to 36 months
Secondary	Mean Dose Proportionality of JZP898 and Activated IFNa		Up to 36 months
Secondary	Pharmacokinetic Parameter: Accumulation ratio for Cmax		Up to 36 months
Secondary	Pharmacokinetic Parameter: Accumulation Ratio for AUC		Up to 36 months
Secondary	Mean JZP898 and Activated IFNa Concentrations		Up to 36 months
Secondary	ORR As Assessed by the Investigator		Up to 36 months
Secondary	Duration of Response (DoR) As Assessed by the Investigator		Up to 36 months
Secondary	Disease Control Rate (DCR) As Assessed by the Investigator		Up to 36 months
Secondary	Progression-free Survival (PFS) As Assessed by the Investigator		Up to 36 months
Secondary	Overall Survival (OS)		Up to 36 months
Secondary	Incidence of ADAs towards JZP898		Up to 36 months
Secondary	Changes in tumor immune cell profile in response to monotherapy and combination therapy as measured by gene expression (nanoString)		Up to 36 months