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

Jazz Pharmaceuticals

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor; Metastatic Solid Tumor

Treatments: Drug: Pembrolizumab; Drug: JZP898

Study type: Interventional

Funder types: Industry

Identifiers

NCT06108050

MK-3475-F62 (Other Identifier)

JZP898-101

KEYNOTE-F62 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 177 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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177 participants in 3 patient groups

Part A1 Dose Exploration: JZP898 monotherapy

Experimental group

Treatment:

Drug: JZP898

Part A2 Dose Exploration: JZP898 in combination with pembrolizumab

Experimental group

Treatment:

Drug: Pembrolizumab

Drug: JZP898

Part B Combination Expansion: JZP898 in combination with pembrolizumab

Experimental group

Treatment:

Drug: Pembrolizumab

Drug: JZP898