SRK-181 Alone or in Combination With Anti-PD-(L)1 Antibody Therapy in Patients With Locally Advanced or Metastatic Solid Tumors (DRAGON)

Exclusion Criteria

• •* Patients must have received one prior line of anti-PD-1 treatment (alone or in combination with other therapy) and have had disease progression clinically or radiographically on the anti-PD-1 treatment.
• •* Up to one line of treatment are allowed between the last dose of anti-PD-1 and enrollment.
• •* For patients with primary oropharyngeal cancer, patients must have results from testing of human papillomavirus (HPV) or P16 status.
• •For Part B Cohort Any Other (enrollment complete): Patient must be diagnosed with any other solid tumor type that is not NSCLC, UC, MEL, or ccRCC for which the patient has had a history of primary anti PD (L)1 antibody nonresponse, presenting the best response (based upon the Investigator's assessment) as progressive disease, after prior anti-PD-(L)1 antibody therapy (alone or in combination with other therapy) currently approved for that tumor indication
• •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed at Screening.
• •Patient must have an Eastern Cooperative Oncology Group performance status (PS) 0-1.
• •Patient must have a predicted life expectancy of ≥ 3 months.
• •Women of child-bearing potential (WOCBP) must have a negative urine or serum pregnancy test up to 24 hours prior to first dose of SRK-181.
• •WOCBP and males with female partners of childbearing potential must agree to use adequate birth control throughout their participation and for 90 days following the last dose of SRK-181.
• •For Part A1 only:
• •* Patient has had anti-PD-(L)1 antibody therapy ≤ 28 days prior to the first dose of SRK-181.
• •* Patient is receiving concurrent anti-cancer treatment, including anti-PD-(L)1 antibody therapy, either approved or investigational, within 28 days prior to the first dose of SRK-181.
• •For Part A2 and Part B only:
• •* Patient is receiving concurrent anti-cancer treatment, with the exception of an anti-PD-(L)1 antibody therapy for Part A2 or Part B, either approved or investigational, within 28 days prior to the first dose of SRK-181.
• •* Patient has received biologic therapy (except for anti-PD-(L)1 antibody therapy for Part A2 or Part B), \<28 days prior to the first dose of SRK-181.
• •* Patient has received systemic cytotoxic chemotherapy (except for in combination with anti-PD-(L)1 antibody therapy) \<28 days prior to the first dose of SRK-181.
• •* Patient has received targeted small molecule therapy within 5 half-lives of the compound prior to the first dose of SRK-181.
• •* Patient has a history of intolerance or treatment discontinuation due to severe irAE or other adverse reaction from prior anti-PD-(L)1 antibody therapy.
• •Patient has a hypersensitivity to anti-PD-(L)1 antibody therapy.
• •Patient has the documented presence of neutralizing ADA to anti-PD-(L)1 antibody therapy.
• •Patient has a diagnosis of immunodeficiency, either primary or acquired.
• •Patient is symptomatic or has uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation.
• •Patient has current second malignancy at other sites (exceptions: adequately treated in situ carcinoma \[e.g., cervical\], non-MEL skin cancer, bilateral synchronous discordant breast cancer, or indolent prostate cancer under observation). A past history of other malignancies is allowed as long as patient has been free of recurrence for ≥ 2 years, or if the patient has been treated with curative intent within the past 2 years and, in the opinion of the Investigator, is unlikely to have a recurrence.
• •Women who are pregnant or breastfeeding.