A Dose Escalation and Cohort Expansion Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors or Non-Hodgkin Lymphoma

Open to people ages 12 years and up

• Males or females ≥ 18 years old (Parts 1 and 2A); males or females ≥ 12 years old and with a body weight ≥ 40 kg are eligible to enroll with tumor types including soft-tissue sarcomas, Ewing's sarcoma, alveolar rhabdomyosarcoma, NUT midline carcinoma (NMC), or chordoma (Part 2B)
• Willing and able to provide consent (and assent for participants between the ages of 12-18)
• Part 1: Participants who meet at least 1 of the following criteria:
  1. Any relapsed/refractory (R/R) solid tumor with readily accessible biopsy sites and consenting to 1 baseline and 1 on-treatment biopsy.
  2. Tumor type of interest (see list below) with measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) AND at least 1 RECIST measurable scan prior to the most recent scan to document the rate of tumor growth before the initiation of study treatment. Tumor types of interest (R/R without other available therapeutic options) are:
     1. Small cell lung cancer (SCLC)
     2. Epithelial ovarian cancer, triple-negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC) with documented MYC copy number gain or overexpression as determined in a certified laboratory using a CAP Laboratory Accreditation (CAP/CLIA) (or equivalent) assay or as assessed using an investigational Ventana anti-c-MYC antibody (Y69) clinical trial assay in a central laboratory (Roche CDx CAP/CLIA Laboratory)
     3. Diffuse large B-cell lymphoma with documented MYC translocation or Burkitt's lymphoma (as determined by local testing)
     4. Sarcoma with documented transcription factor fusion (as determined by local testing)
     5. Chordoma, NUT midline carcinoma, or adenoid cystic carcinoma

• Part 2A: Participants with histologically or cytologically confirmed solid tumors who have failed, are intolerant to or are considered ineligible for standard-of-care anti-cancer treatments.

  Note: All Part 2, Cohort A, participants will require documented MYC copy number gain or overexpression in tumor or liquid biopsy as determined in a certified laboratory using a CAP/CLIA (or equivalent) assay or as assessed using an investigational Ventana anti-c-MYC antibody (Y69) clinical trial assay in a central laboratory (Roche CDx CAP/CLIA Laboratory). This cohort will include approximately 10 participants with each of the following malignancies: NSCLC, triple-negative breast cancer and ovarian cancer.

• Part 2B: Participants with histologically or cytologically confirmed SCLC or soft-tissue sarcomas with defined transcription factor oncogenic drivers as determined locally, including (but not limited to) chordomas, Ewing's sarcoma or alveolar rhabdomyosarcoma as well as NUT midline carcinomas (NMC) or adenoid cystic carcinomas, without access to or intolerant of other approved therapies.
• Access to a tumor sample for central laboratory testing
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
• Evaluable or measurable disease, per RECIST 1.1 for solid tumors or the Lugano Classification for non-Hodgkin lymphoma
• Adequate bone marrow and organ function
• Recovery from treatment-related toxicities from prior therapies to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade ≤ 1 or to baseline level
• Must agree to use highly effective birth control during the trial and for at least 3 months after the last dose of study drug; female participants cannot be pregnant or breastfeeding

• Any other anti-cancer therapies including chemotherapy, immunotherapy, or hormonal therapy within 4 weeks or 5 half-lives (whichever is shorter)
• History of surgery (except for diagnostic purposes) or non-palliative radiotherapy within 4 weeks
• History of allogeneic transplantation within 6 months
• Active central nervous system (CNS) involvement by the underlying malignancy; previously treated CNS metastatic disease is permitted with magnetic resonance imaging (MRI) documentation of stable disease for at least 3 months prior to study start
• History of stroke or intracranial hemorrhage within ≤6 months
• History of seizure disorder, ie, recurrent seizures with an underlying etiology and requiring ongoing anti-epileptic medication
• Current use of medications associated with seizure risk unless approved by Medical Monitor
• Active infections requiring systemic antibiotic, antiviral or antifungal therapy
• Known active coronavirus disease 2019 (COVID-19)
• Clinically significant heart disease
• Uncontrolled hypertension
• Prolongation of QT interval at baseline
• Known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection
• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease