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

Sponsor

Jazz Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06108050

Collaborator

(none)

177

Enrollment

Locations

Arms

54.5

Anticipated Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor Metastatic Solid Tumor	Drug: JZP898 Drug: Pembrolizumab	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

177 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Nov 15, 2023

Anticipated Primary Completion Date :

Nov 30, 2027

Anticipated Study Completion Date :

May 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A1 Dose Exploration: JZP898 monotherapy	Drug: JZP898 Investigational drug monotherapy
Experimental: Part A2 Dose Exploration: JZP898 in combination with pembrolizumab	Drug: JZP898 Investigational drug monotherapy Drug: Pembrolizumab Approved anti-PD1 antibody
Experimental: Part B Combination Expansion: JZP898 in combination with pembrolizumab	Drug: JZP898 Investigational drug monotherapy Drug: Pembrolizumab Approved anti-PD1 antibody

Arm

Intervention/Treatment

Experimental: Part A1 Dose Exploration: JZP898 monotherapy

Drug: JZP898

Investigational drug monotherapy

Experimental: Part A2 Dose Exploration: JZP898 in combination with pembrolizumab

Drug: JZP898

Investigational drug monotherapy

Drug: Pembrolizumab

Approved anti-PD1 antibody

Experimental: Part B Combination Expansion: JZP898 in combination with pembrolizumab

Drug: JZP898

Investigational drug monotherapy

Drug: Pembrolizumab

Approved anti-PD1 antibody

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

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

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:

NSCLC: eligible for platinum-based therapy and received platinum-based therapy prior to inclusion in the study.
HNSCC: eligible for platinum therapy and received platinum-based therapy prior to inclusion in this study.
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tennessee Oncology	Nashville	Tennessee	United States	37203
2	Texas Oncology - Baylor Charles A Sammons Cancer Center	Dallas	Texas	United States	75246
3	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031

Sponsors and Collaborators

Jazz Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jazz Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT06108050

Other Study ID Numbers:

JZP898-101

First Posted:

Oct 30, 2023

Last Update Posted:

Oct 30, 2023

Last Verified:

Oct 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Jazz Pharmaceuticals

Advanced Solid Tumor

Metastatic Solid Tumor

JZP898

Additional relevant MeSH terms:

Neoplasms

Pembrolizumab

Study Results

No Results Posted as of Oct 30, 2023