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

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) (or highest cleared dose level) and safety profile of JZP898.
• Part A2 - a combination dose exploration of JZP898 plus pembrolizumab to determine the CombiRD (combination recommended dose for expansion).

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 CombiRD identified in Part A2.

Inclusion criteria

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

• Previously treated participants with solid tumors that are amenable to CPI therapy (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.
• 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:

• 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 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 from previous therapy that is > 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 a stem cell/solid organ transplant.
• Receipt of prior IFNα therapy