Overview

This is a multi-center, open-label, Phase 1, first-in-human (FIH), dose-escalation, and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SRK-181 administered alone and in combination with anti-PD-(L)1 therapy in adult patients with locally advanced or metastatic solid tumors. The study is divided into 3 treatment parts (Part A1, Part A2, and Part B) and a Long-Term Extension Phase (LTEP).

Eligibility

Key Inclusion Criteria:

• Patient has a histologically documented solid tumor that is metastatic or locally advanced, for which SoC therapy does not exist, has failed in the patient, or is not tolerated by the patient, or for which the patient has been assessed by the Investigator as not being a suitable candidate or otherwise ineligible for the SoC therapy.
• For Part A2 and Part B:
• Patient must have a history of primary anti-PD-(L)1 antibody nonresponse presenting (based upon the Investigator's assessment) either as progressive disease or stable disease (e.g., not improving, but also not worsening, clinically or radiographically) after at least 3 cycles of treatment with an anti-PD-(L)1 antibody therapy (alone or in combination with chemotherapy) approved for that tumor type.
• Patient must have received their most recent dose of anti-PD-(L)1 antibody therapy within 6 months of enrollment.
• For NSCLC patients who have genomic tumor aberrations for which a targeted therapy is available (e.g., anaplastic lymphoma kinase, EGFR), these patients must have progressed on an approved therapy for these aberrations or did not tolerate an approved therapy for these aberrations, or were not considered suitable candidates/ were otherwise ineligible for an approved therapy for these aberrations.
• 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 pregnancy test within 72 hours prior to first administration of SRK-181 and a negative urine pregnancy test on the first day of dosing.
• WOCBP and males with female partners of child-bearing potential must agree to use adequate birth control throughout their participation and for 90 days following the last dose of SRK-181.

Key Exclusion Criteria:

• For Part A1 only:
• Patient has had anti-PD-(L)1 antibody therapy 28 days prior to enrollment.
• Patient is receiving concurrent anticancer treatment, including anti-PD-(L)1 antibody therapy, either approved or investigational, within 28 days prior to administration of SRK-181.
• For Part A2 and Part B only:
• Patient is receiving concurrent anticancer 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 administration 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 administration of SRK-181.
• Patient has received systemic cytotoxic chemotherapy (except for in combination with anti-PD-(L)1 antibody therapy) <28 days prior to administration of SRK-181.
• Patient has received targeted small molecule therapy within 5 half-lives of the compound prior to administration 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.