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

Eligibility: Inclusion Criteria
  •   * Adult >= 18 years of age
  •   * Histological or cytological diagnosis of advanced or metastatic solid tumor.
  •    1. 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.
  •    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 from previous therapy that is > Grade 1.
  •   * Hypersensitivity to mAb, IFN¿, 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 IFN¿ therapy