The study will determine the recommended Phase 2 dose (RP2D) of an active drug administered as monotherapy and in combination with an active drug as well as to assess the safety, pharmacokinetics (PK), and preliminary efficacy of an active drug alone and in combination with an active drug. The study will consist of 2 phases: dose escalation and dose expansion.
18 Years and older.
- For Dose Escalation only: Participants with an advanced solid tumor who are considered
refractory to or intolerant of all existing therapy(ies) known to provide a clinical
benefit for their condition. Additionally, participants who have been offered standard
therapies and refused, or who are considered ineligible for standard therapies, may be
eligible for this study on a case-by-case basis, after discussion with and agreement
from the sponsor. Participants with pancreatic adenocarcinoma, urothelial cancer,
hepatocellular carcinoma (HCC), or head and neck squamous cell carcinoma (HNSCC) who
are being considered for the dose escalation cohorts must also meet the histology
specific eligibility criteria described below for dose expansion.
- For Dose Expansion only participants must meet criteria specific to the type of
- Pancreatic adenocarcinoma and have disease progression during or after 1 systemic
therapy (gemcitabine monotherapy or in combination with other agents, FOLFIRINOX
[or another regimen including both 5-fluorouracil and oxaliplatin], capecitabine
monotherapy or in combination with other agents) administered in the adjuvant,
locally advanced, or metastatic setting. If the therapy was used in an adjuvant
setting, disease progression must have occurred within 6 months of completing
- Urothelial cancer of the bladder and urinary tract and must have progressed
following treatment with a platinum-based regimen (administered in any line of
therapy) and a programmed death 1/programmed death ligand 1 (PD1/PDL1) antagonist
administered in the recurrent or metastatic setting (progression following a
PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months
of the last dose of anti-PD1 or anti-PDL1 therapy).
- HCC and must have disease progression during or after 1 prior line of systemic
- HNSCC (arising from the oral cavity, oropharynx, hypopharynx, or larynx) and must
have progressed following treatment with platinum-based regimen (administered in
any line of therapy) and a PD1/PDL1 antagonist administered in the recurrent or
metastatic setting (progression following a PD1/PDL1 antagonist is defined as
unequivocal progression on or within 3 months of the last dose of anti-PD1 or
- Microsatellite stable colorectal cancer (MSS-CRC) [unselected] participants with
microsatellite stable or mismatch repair proficient colorectal adenocarcinoma (as
determined by polymerase chain reaction (PCR)/Next-Generation sequencing (NGS) or
immunohistochemistry (IHC), respectively) who have received 1-2 prior
- Non-small cell lung cancer (NSCLC) relapsed/refractory (R/R): Participants with
histologically or cytologically confirmed advanced or metastatic NSCLC who have
received 1 prior line of chemotherapy and 1 prior anti-PD-(L)1 antibody,
administered either concurrently or sequentially in the metastatic setting.
- NSCLC (1L PD-L1 high) with liver metastasis enrichment: Participants with
histologically or cytologically confirmed advanced or metastatic NSCLC, with high
expression PD-L1 as defined by Tumor Proportion Score (TPS) >=50%, no known
(EGFR) mutations or ALK gene rearrangements, who have received no prior therapy
in the advanced or metastatic setting.
- MSS-CRC (CMS4 enriched): Participants with microsatellite stable or mismatch
repair proficient colorectal adenocarcinoma who have received prior
fluorouracil-based combination chemotherapy regimens including oxaliplatin and
irinotecan (with or without VEGF and/or EGFR targeted agents) and with a CMS4
subtype as determined by NGS of tumor biopsies. Archival tissue must be submitted
for assessment of CMS4 subtype status during prescreening.
- Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0
- Participant has adequate bone marrow, renal, hepatic, and coagulation function.
- Must have a viral status consistent with the requirements described in the protocol
specific to type of cancer and stage of study (Dose Escalation or Dose Expansion).
- For Dose Expansion only:
- Participants with HCC, pancreatic adenocarcinoma, or MSS-CRC having prior
exposure to a prior PD-1/PD-L1 antagonist in any line of therapy.
- Participants (except for participants with urothelial cancer or HNSCC) who have
had prior exposure to immunotherapies as listed in the protocol.
- Has received anticancer therapy including chemotherapy, immunotherapy, radiation
therapy, biologic, herbal therapy, or any investigational therapy within a period of 5
half-lives or 28 days (whichever is shorter), prior to the first dose of the study
- Participant has unresolved AEs > Grade 1 from prior anticancer therapy except for
- Has a history of primary immunodeficiency, bone marrow transplantation, solid organ
transplantation, or previous clinical diagnosis of tuberculosis.
- Has a known uncontrolled metastases to the central nervous system (with certain
- Current or prior use of immunosuppressive medication within 14 days prior to the first
dose of the study drug.
- Has clinically significant uncontrolled condition(s).
- History of inflammatory bowel disease, interstitial lung disease or pneumonitis,
myocarditis, Stevens-Johnson syndrome, toxic epidermal necrolysis or drug reaction
with eosinophilia and systemic symptoms (DRESS).
- Live vaccine administration <= 28 days prior to the first dose of study drug.