BI-1910 as a Single Agent and in Combination With Pembrolizumab for the Treatment of Advanced Solid Tumors

Prior treatment

• Needs doses of prednisolone \>10 mg daily (or equipotent doses of other corticosteroids) while on the trial other than as premedication.
• Has received the following:
  • Chemotherapy or small molecule anti-cancer therapy products within 4 weeks, or 5 half-lives of the respective drug whichever is longer, of first dose of BI-1910.
  • Radiotherapy within 2 weeks of first dose of BI-1910. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) for non-CNS disease.
  • Subjects who have previously had radiation pneumonitis are not allowed.
  • Immunotherapy within 4 weeks prior to the first dose of BI-1910.
• Has had Grade ≥3 autoimmune manifestations of previous immune checkpoint inhibitor treatments (e.g., anti-PD-1, anti-PD-L1, or anti-CTLA-4).
• Has had major surgery from which the subject has not yet recovered.
• Is at high medical risk because of nonmalignant systemic disease including severe active infections on treatment with antibiotics, antifungals, or antivirals other than the ones considered adequate for treatment of HBV.
• Has had an allogenic tissue/solid organ transplant.
• Has received a live vaccine within 30 days before the first dose of study treatment.
• Is participating or planning to participate in another interventional clinical trial or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to first dose of study treatment.
• Has a known additional malignancy of another type, with the exception of adequately treated cone-biopsied carcinoma in situ and basal or squamous cell carcinoma of the skin. Male subjects with asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for \>1 year prior to start of study treatment are eligible.
• Has a confirmed diagnosis of primary immunodeficiency or an acquired condition that leads to an immunodeficiency disorder or taking any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.

Other illness

• Has known or suspected hypersensitivity to BI-1910 or pembrolizumab.
• Has cardiac or renal amyloid light-chain amyloidosis.
• Has not recovered from AEs to at least Grade 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v5.0 or higher).
• Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active, known, or suspected autoimmune disease.
• Has presence of chronic graft versus host disease.
• Is positive for Human Immunodeficiency Virus (HIV).
• Has history of chronic HBV or HCV infections.
• Has a history of active tuberculosis (Bacillus tuberculosis).
• Has uncontrolled or significant cardiovascular disease.
• Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the trial.

Lab values

• Is a female subject and has the ability to become pregnant (or already pregnant or lactating/breastfeeding). However, those female subjects who have a negative serum or urine pregnancy test up to 72 hours prior to their first dose of study treatment and agree to use a highly effective method of birth control for 4 weeks before entering the trial, during the trial, and for 12 months after their last dose of study treatment are considered eligible.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.

Other

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Is a male subject with partner(s) of childbearing potential (unless he agrees to use a barrier method of contraception \[condom plus spermicidal gel\] with the female partner(s) who are using one highly effective method of contraception during the trial and for 12 months after completing treatment).

• Is willing and able to provide signed informed consent for the trial.
• Is ≥18 years of age on the day of signing the informed consent form.
• Has a histologically-confirmed advanced/metastatic solid tumor.
• Has received standard of care and progressed or is intolerant of, or is not eligible to receive standard of care antineoplastic therapy.
• Has at least 1 measurable disease lesion as defined by RECIST v1.1.
• Must be willing to provide tumor biopsies as specified in the schedule of assessments
• Has a life expectancy of ≥12 weeks.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate organ function as confirmed by laboratory values.