Inclusion Criteria:
1. Informed consent signed by the participant prior to conducting study-specific procedures
2. ≥18 years of age
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
4. Histological or cytological diagnosis of:
Part A: advanced B-cell lymphomas or solid tumors, of the following subtypes:
B-cell Lymphomas:
* Mantle cell lymphoma (MCL)
* Diffuse large B-cell lymphoma (DLBCL) (including Richter's transformation)
* Follicular lymphoma
* Small lymphocytic lymphoma (SLL)
Solid Tumors:
* Pancreatic cancer
* Non-squamous non-small cell lung cancer (NSCLC)
* Malignant mesothelioma
* Epithelial ovarian cancer. Participants with fallopian tube and/or peritoneal malignancies are also eligible.
* Triple-negative breast cancer.
* Liposarcoma
Other, unlisted histologies, if approved by the Sponsor Medical Monitor
Part B Cohorts B1, B2, and B3:
Histological or cytological diagnosis of the cohort-specific disease indication. Indications may include those listed in Inclusion Criterion 4.a
5. Participants must have adequate organ function.
6. Participants must have a negative pregnancy test, be willing to practice highly effective methods of birth control, use condoms, and refrain from oocyte/sperm donation, as applicable, as detailed in the protocol.
7. Participants must be refractory to or have relapsed after at least one prior standard therapeutic regimen. Participants must be relapsed or refractory to, have developed an intolerance to, or not be candidates for available therapies with established benefit. Participants with B-cell malignancies should have received at least two lines of therapy, including available therapies with established benefit. Participants with SLL should have received at least three prior lines of therapy.
8. Participants must have measurable disease as per the relevant response assessment framework: Lugano Classification for lymphoma (except SLL) , per iwCLL criteria for SLL , and per RECIST v.1.1 for solid tumors.
Exclusion Criteria:
1. Previously treated with an ADC with a topoisomerase-1 inhibitor payload, except: Participants with triple negative breast cancer may have received up to one prior ADC with a topoisomerase-1 inhibitor payload.
2. Previously received a ROR1-targeted therapy (eg, ADC, cell therapy, or monoclonal antibody).
3. History of an anaphylactic reaction to irinotecan or ≥ grade 3 GI toxicity to prior irinotecan.
4. Life expectancy \< 12 weeks.
5. Prior solid organ transplant.
6. Participants with symptomatic ascites or pleural effusion. Participants who are clinically stable for at least 2 weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis or catheter) are eligible.
7. Participant has a known active central nervous system (CNS) primary tumor or metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no radiological evidence of new or enlarging brain metastases, and are off steroids or on a stable dose up to an equivalent of prednisone 10 mg/day for at least 15 days prior to first dose of study medication. Participants who have symptoms consistent with CNS metastasis must have a negative magnetic resonance imaging (MRI) or other clinically appropriate imaging study if the participant is not able to undergo contrast-enhanced MRI and approved by the Sponsor Medical Monitor during the screening period.
8. Participant has a known history of malignant primary brain tumor, or another primary solid or hematologic malignancy (other than that under study), unless the participant has undergone potentially curative therapy with no evidence of that disease for at least 2 years. Exception: The time requirement does not apply to participants who underwent successful definitive resection of certain cancers.
9. Participant has certain other significant medical conditions including cardiac, pulmonary, and infectious disease as detailed in the protocol.
10. Participant is pregnant, breastfeeding, or expecting to conceive within the projected duration of the study.
