A Study of the Safety and Tolerability of ABBV-621 in Participants With Previously Treated Solid Tumors and Hematologic Malignancies

Inclusion Criteria:

- Must have a diagnosis of a solid tumor (except primary brain tumors), acute myeloid
leukemia (AML), or non-Hodgkin lymphoma (NHL); NHL may be of any subtype for Dose
Escalation but is limited to diffuse large B-cell lymphoma (DLBCL) for those enrolled
to the cohort evaluating the combination of ABBV-621 and venetoclax. Subjects in the
Dose Optimization solid tumor cohorts must have either colorectal cancer with
documented KRAS mutations (as determined by local testing), or pancreatic cancer
(irrespective of mutational status).

- Participant in dose escalation or dose optimization cohort must have received at least
one prior systemic therapy, and must have relapsed or progressed after, or failed to
respond to any/all available effective therapy or therapies.

- Must have measurable disease (by Response Evaluation Criteria In Solid Tumors [RECIST]
1.1 for those with solid tumors; by Lugano classification for those with NHL), except
those with AML, who must have histologically confirmed relapsed or refractory disease.

- Must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 - 2.
Participants in chemotherapy combination cohorts must have ECOG Performance Score of 0
- 1.

- Must have adequate hematologic, renal and hepatic function.

- Participants in chemotherapy combination cohorts must have metastatic or advanced
unresectable colorectal cancer with documented KRAS mutation or pancreatic
adenocarcinoma.

- Participant in chemotherapy combination cohort with pancreatic adenocarcinoma must be
treatment naive.

Exclusion Criteria:

- Participants with history of brain metastases who have not shown clinical and
radiographic stable disease for at least 28 days after definitive therapy.

- Presence of primary hepatobiliary malignancy, including cholangiocarcinoma or
hepatocellular carcinoma, gallbladder carcinoma, cancer of ampulla of Vater.

- Receipt of any systemic anti-cancer agent, including investigational anti-cancer
products, within 21 days prior to study drug administration or 3 half-lives, whichever
is longer.

- Participant with a history of cirrhosis or other indication of significant possible
hepatic dysfunction. Note: Those with non-alcoholic steatohepatitis (NASH) should be
discussed with the AbbVie TA MD before enrollment.

- Participant with a positive diagnosis of hepatitis A, B, or C.

- CRC chemotherapy cohort only: Participant with minor surgical procedures, such as fine
needle aspirations or core biopsies, within 7 days prior to first dose of study drug
are excluded.

- Participants in CRC chemotherapy combination cohort only: cardiomyopathy,
coronary/peripheral artery bypass graft, aneurysm or aneurysm repair, angioplasty,
pulmonary hypertension, cerebrovascular accident or transient ischemic attack, within
1 year of first dose of study drug.

- Chemotherapy combination pancreatic adenocarcinoma participants only: history of
pneumonitis.

- Chemotherapy combination CRC participants only: Prior receipt of an irinotecan-based
chemotherapy.

- Chemotherapy combination CRC participants only: history of Gilbert's syndrome or
UG1T1A1 genotypes.

- Chemotherapy Combination CRC Participants Only: Clinically significant conditions that
may place the participant at higher risk with anti-angiogenic therapy.