Phase 1, first-in-human, open-label dose escalation and cohort expansion study of KB-0742 in patients with relapsed or refractory solid tumors or non-Hodgkin lymphoma

Part 1: Dose Escalation. The primary objective of Part 1 of this study is to evaluate the
safety and tolerability of KB-0742 in participants with relapsed or refractory (R/R) solid
tumors or non-Hodgkin lymphoma (NHL).

Part 2: Cohort Expansion. The primary objective of Part 2 of this study is to further
evaluate the safety and tolerability of KB-0742 in defined participant cohorts.

Inclusion Criteria:

- 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 to <18)

- Part 1: Participants who meet at least 1 of the following criteria:

1. Any R/R solid tumor with, in the opinion of the investigator at the time of
screening has at least 1 readily accessible biopsy site(s) and who consents to 1
baseline and 1 on-treatment biopsy. If the feasibility of obtaining biopsies
changes after the participant has been consented due to changes in clinical or
surgical considerations and the participant otherwise meets all eligibility
criteria, they may still enroll/or continue on study.

2. Tumor type of interest (see list below) with measurable disease per Response
Evaluation Criteria in Solid Tumors 1.1 (RECIST) 1.1 or Positron Emission
Tomography (PET) Response Criteria in Solid Tumors (PERCIST) 1.0 for solid tumors
or by Lugano Classification or Modified Weighted Assessment Tool (mSWAT) for NHL
AND at least 1 measurable scan per one of the above criteria 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. SCLC

2. Epithelial ovarian cancer, TNBC, or NSCLC

3. Other epithelial solid tumor with evidence of MYC copy number gain based on
local testing

4. Diffuse large B-cell lymphoma with documented MYC translocation or Burkitt's
lymphoma (as determined by local testing)

5. Sarcoma of histologic subtypes known to be associated with transcription
factor fusion, specifically: i. Myxoid/round cell sarcoma ii. Clear cell
sarcoma iii. Desmoplastic small round cell tumor iv. Low grade fibromyxoid
sarcoma v. Extraskeletal myxoid chondrosarcoma vi. Ewing sarcoma vii.
Alveolar rhabdomyosarcoma

6. Chordoma, NUT midline carcinoma, or adenoid cystic carcinoma

- Part 2, Cohort A: 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: Part 2, Cohort A, will include
participants with relapsed or refractory solid tumors including NSCLC, TNBC and
ovarian cancer.

- Part 2, Cohort B: Participants with histologically or cytologically confirmed tumor
type of interest without access to or intolerant of other approved therapies,
including SCLC.

- For both Parts 1 and 2:

- 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 or PERCIST 1.0 for solid tumors or the
Lugano Classification or mSWAT for NHL

- 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

Exclusion Criteria:

- 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.
Participants with SCLC with prior treatment with stereotactic radiosurgery or whole
brain radiation therapy for CNS metastatic disease 2 weeks or more before study start
may be considered eligible for enrollment if assessed stable and meet all other
eligibility criteria.

- History of stroke or intracranial hemorrhage within ≤6 months

- History of seizure or seizure disorder, ie, recurrent seizures with an underlying
etiology and requiring ongoing anti-epileptic medication

- Current use of medications associated with seizure risk

- 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