AB122 Platform Study

Inclusion Criteria:

• Is male or female aged ≥ 18 years at the time of informed consent; Willing and ableto comply with scheduled visits and study procedures (except for Cohort E-2);

• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1before administration of study treatment;

• Has adequate organ function as defined by the following criteria:

• AST and ALT ≤ 3 × ULN; or if a patient with documented liver metastases, ASTand ALT ≤ 5 × ULN

• T-Bil of ≤ 1.5 × ULN

• ANC ≥ 1500 /mm3 (ie, ≥ 1.5 × 109 /L by International System of Units [SI]) (excluding measurements obtained within 7 days after administration ofgranulocyte colony-stimulating factor [G-CSF])

• Platelet count ≥ 100000 /mm3 (SI: ≥ 100 × 109 /L) (excluding measurementsobtained within 7 days after a transfusion of platelets)

• Hemoglobin value of ≥ 9.0 g/dL excluding measurements within 4 weeks after atransfusion of packed red blood cells (RBCs) or whole blood

• Has a life expectancy of at least 90 days;

Cohort A-1 and A-2

• Japanese male and female;

• Has a histologically or cytologically confirmed diagnosis of solid tumor;

• Has disease progression after standard treatment for advanced or metastatic disease,are intolerant to the standard treatment;

Cohort B-1

• Has a histologically or cytologically confirmed diagnosis of PDAC;

• Has disease progression after or intolerant to one prior systemic chemotherapy foradvanced or metastatic disease

Cohort B-2

• Has a histologically or cytologically confirmed diagnosis of CRC.

• Has been received one regimen of standard chemotherapy for advanced or metastaticdisease, and was refractory or intolerant to the chemotherapy

Cohort B-3 - Has a histologically or cytologically confirmed non-squamous NSCLC;

• Has been received one or two regimen of standard chemotherapy for advanced ormetastatic disease, and was refractory or intolerant to the standard treatment

• Has been most recently received regimen including an ICI (anti PD-1 antibodies, antiPD-L1 antibodies or anti CTLA-4 antibodies) and platinum-based chemotherapy incombination or in sequence (i.e., platinum-based chemotherapy followed by checkpointinhibitor therapy), and all of the following criteria must be met:

• Received at least 2 doses at the most recent ICI therapy

• Radiographic complete response or partial response based on investigatorassessment with ICI therapy

• Documented radiographic disease progression with above most recently receivedregimen

Cohort C-1

• Has unresectable advanced or recurrent gastric cancer or gastroesophageal junctioncancer as pathologically confirmed adenocarcinoma

• Gastroesophageal junction cancer is defined as a tumor with an epicenter that islocated within 2 cm proximal to and distal from the esophagogastric junction (theboundary of esophageal and gastric muscularis).

• Has received 2-4 standard regimens listed below and has demonstrated diseaseprogression according to imaging test during the most recent treatment or within 12weeks after the final dose (The patient is eligible if the treatment is discontinuedowing to SAEs, allergic reactions, or neurotoxicities.):

• fluoropyrimidines and platinum

• taxane or irinotecan

• ramucirumab

Cohort C-2

• Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (allother histological types are excluded)

• RAS status must have been previously determined (mutant or wild-type) based on localassessment of tumor biopsy; Wild type is defined as v-Ki-ras2 Kirsten rat sarcomaviral oncogene homolog (KRAS) (exon 2, 3 and 4) and neuroblastoma RAS viral (v-ras)oncogene homolog (NRAS) (exon 2, 3 and 4) wild type. [Mutant is defined as at leastKRAS or NRAS mutant (any exon, any mutation)].

• Has received at least 2 prior chemotherapy regimens for the treatment of advancedCRC and had demonstrated disease progression according to imaging test during themost recent treatment or within 12 weeks after the final dose , or intolerance totheir last regimen, and all of the following criteria must be met:

• Prior treatment regimens must have included a fluoropyrimidine, irinotecan,oxaliplatin, an anti-VEGF monoclonal antibody

• For RAS wild-type patients, an anti-EGFR monoclonal antibody must have includedin addition to above

Cohort D-1

• Has histologically confirmed advanced or metastatic NSCLC regardless of histologictype.

• Has PD-L1 (≥ 50% tumor proportion score) in tumor tissue sample as determined at alocal laboratory.

Cohort D-2

• Has histologically diagnosed advanced or metastatic adenocarcinoma or squamous cellcarcinoma of the esophagus.

• No prior therapy for advanced or metastatic disease. • Adjuvant therapy or neoadjuvant therapy is not considered as prior therapy if there is no recurrence duringor within 6 months after completion of the therapy.

Cohort D-3

• Has histologically diagnosed advanced or metastatic adenocarcinoma or squamous cellcarcinoma of the esophagus.

• No prior therapy for advanced or metastatic disease, or refractory or intolerant toat least 1 cycle of standard first-line therapy.

• Treatment discontinued due to intolerable toxicity or because the same drugcannot be re-treated before the disease progresses is considered as intolerableto the previous treatment.

• Adjuvant therapy or neo adjuvant therapy is not considered as prior therapy ifthere is no recurrence during or within 6 months after completion of thetherapy.

Cohort D-4

• Has histologically or cytologically confirmed recurrent or advanced squamous head

• Received at least 2 doses at the most recent ICI therapy
 

• Radiographic complete response or partial response based on investigator
assessment with ICI therapy
 

• Documented radiographic disease progression with above most recently received
regimen
 
 Cohort C-1
 

• Has unresectable advanced or recurrent gastric cancer or gastroesophageal junction
cancer as pathologically confirmed adenocarcinoma
 

• Gastroesophageal junction cancer is defined as a tumor with an epicenter that is
located within 2 cm proximal to and distal from the esophagogastric junction (the
boundary of esophageal and gastric muscularis).
 

• Has received 2-4 standard regimens listed below and has demonstrated disease
progression according to imaging test during the most recent treatment or within 12
weeks after the final dose (The patient is eligible if the treatment is discontinued
owing to SAEs, allergic reactions, or neurotoxicities.):
 

• fluoropyrimidines and platinum
 

• taxane or irinotecan
 

• ramucirumab
 
 Cohort C-2
 

• Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all
other histological types are excluded)
 

• RAS status must have been previously determined (mutant or wild-type) based on local
assessment of tumor biopsy; Wild type is defined as v-Ki-ras2 Kirsten rat sarcoma
viral oncogene homolog (KRAS) (exon 2, 3 and 4) and neuroblastoma RAS viral (v-ras)
oncogene homolog (NRAS) (exon 2, 3 and 4) wild type. [Mutant is defined as at least
KRAS or NRAS mutant (any exon, any mutation)].
 

• Has received at least 2 prior chemotherapy regimens for the treatment of advanced
CRC and had demonstrated disease progression according to imaging test during the
most recent treatment or within 12 weeks after the final dose , or intolerance to
their last regimen, and all of the following criteria must be met:
 

• Prior treatment regimens must have included a fluoropyrimidine, irinotecan,
oxaliplatin, an anti-VEGF monoclonal antibody
 

• For RAS wild-type patients, an anti-EGFR monoclonal antibody must have included
in addition to above
 
 Cohort D-1
 

• Has histologically confirmed advanced or metastatic NSCLC regardless of histologic
type.
 

• Has PD-L1 (≥ 50% tumor proportion score) in tumor tissue sample as determined at a
local laboratory.
 
 Cohort D-2
 

• Has histologically diagnosed advanced or metastatic adenocarcinoma or squamous cell
carcinoma of the esophagus.
 

• No prior therapy for advanced or metastatic disease. • Adjuvant therapy or neo
adjuvant therapy is not considered as prior therapy if there is no recurrence during
or within 6 months after completion of the therapy.
 
 Cohort D-3
 

• Has histologically diagnosed advanced or metastatic adenocarcinoma or squamous cell
carcinoma of the esophagus.
 

• No prior therapy for advanced or metastatic disease, or refractory or intolerant to
at least 1 cycle of standard first-line therapy.
 

• Treatment discontinued due to intolerable toxicity or because the same drug
cannot be re-treated before the disease progresses is considered as intolerable
to the previous treatment.
 

• Adjuvant therapy or neo adjuvant therapy is not considered as prior therapy if
there is no recurrence during or within 6 months after completion of the
therapy.
 
 Cohort D-4
 

• Has histologically or cytologically confirmed recurrent or advanced squamous head
and neck cancer (oropharynx, oral mucosa, hypopharynx, larynx).

• The confirmed status of the human papillomavirus (HPV) in cancers of themid-pharynx.

• Patient background such as combined positive score (CPS) and head and neckcancer treatment guidelines must be taken into account to confirm the validityof enrollment in this cohort.

• No prior therapy for advanced or metastatic disease. • Adjuvant therapy or neoadjuvant therapy is not considered as prior therapy if there is no recurrence duringor within 6 months after completion of the therapy. • Treatment of locally advanceddisease completed more than 6 months prior to the start of study drug administrationis not considered prior therapy.

Cohort D-5

• Has histologically or cytologically confirmed recurrent or advanced squamous headand neck cancer (oropharynx, oral mucosa, hypopharynx, larynx).

• The confirmed status of the HPV in cancers of the mid-pharynx.

• Patient background such as CPS and head and neck cancer treatment guidelinesmust be taken into account to confirm the validity of enrollment in thiscohort.

• No prior therapy for advanced or metastatic disease. • Adjuvant therapy or neoadjuvant therapy is not considered as prior therapy if there is no recurrence duringor within 6 months after completion of the therapy. • Treatment of locally advanceddisease completed more than 6 months prior to the start of study drug administrationis not considered prior therapy.

Cohort D-6

• Has histologically or cytologically confirmed recurrent or advanced squamous NSCLC.

• No prior therapy for advanced or metastatic disease. • Adjuvant therapy or neoadjuvant therapy is not considered as prior therapy if there is no recurrence duringor within 6 months after completion of the therapy.

Cohort D-7

• Has histologically confirmed unresectable or advanced biliary tract cancer (intrahepatic bile duct, extrahepatic bile duct, gallbladder, or duodenal papillaryregion) with a diagnosis of adenocarcinoma or adenosquamous carcinoma.

• No prior therapy for advanced or metastatic disease. • Adjuvant therapy or neoadjuvant therapy is not considered as prior therapy if there is no recurrence duringor within 6 months after completion of the therapy.

Cohort D-8

• Has histologically confirmed unresectable or advanced pancreatic ductaladenocarcinoma (highly differentiated, moderately differentiated, or poorlydifferentiated).

• No prior therapy for advanced or metastatic disease. Adjuvant therapy or neoadjuvant therapy is not considered as prior therapy if there is no recurrence duringor within 6 months after completion of the therapy.

Cohort E-1

• Has a histologically or cytologically confirmed advanced or metastatic NSCLCregardless of histologic type.

• Has PD-L1 (≥ 50% tumor proportion score) in tumor tissue sample as determined at alocal laboratory (except for tolerability part).

• Has been received 1-4 regimen for advanced or metastatic disease

• Has been received one regimen of ICI monotherapy or combination therapy (anti PD-1antibodies, anti PD-L1 antibodies or anti CTLA-4 antibodies), and all of thefollowing criteria must be met:

• Received at least 2 doses of the ICI therapy

• Documented radiographic disease progression with or after ICI therapy

Cohort E-2

• Has a histologically or cytologically confirmed advanced or metastatic ASPS

• Is male or female aged ≥ 16 years at the time of informed consent; Willing and ableto comply with scheduled visits and study procedure

Exclusion Criteria:

• History or current evidence of cardiac arrhythmia and/or conduction abnormality: Anyfactor that can increase the risk of corrected QT interval (QTc) prolongation orrisk of arrhythmic events such as heart failure, congenital long QT syndrome, etc.;

• Treatment with any of the following within the specified time frame prior to the dayon which study treatment is scheduled to be started:

• Major surgery within 4 weeks (the surgical incision should be fully healedprior to the day on which study treatment is scheduled to be started);

• Extended-field radiotherapy within 4 weeks or limited-field radiotherapy within 2 weeks;

• Any anticancer therapy within 2 weeks;

• Any investigational agent received within 5 half-lives of the drug or 4 weeks,whichever shorter;

• Unresolved toxicity of ≥ Grade 2 attributed to any prior therapies (excludinganemia, peripheral sensory neuropathy, alopecia and skin pigmentation);

• A serious illness or medical condition(s) including, but not limited to, thefollowing specific medical conditions:

• Known acute systemic infection;

• Known medical history of interstitial lung disease/ drug-induced interstitiallung disease/ radiation pneumonitis which required steroid treatment/ anyevidence of clinically active interstitial lung disease;

• Myocardial infarction, severe/unstable angina, symptomatic congestive heartfailure (New York Heart Association [NYHA] class III or IV, Appendix A) withinthe previous 6 months; if > 6 months, cardiac function must bewithin normal limits and the patient must be free of cardiac-related symptoms;

• Known severe chronic kidney disease;

• Known positivity of human immunodeficiency virus (HIV) antibody, hepatitis Bsurface antigen (HBsAg) or hepatitis C virus (HCV) antibody in baseline virustest. In addition, the patient who is known negative in HCV ribonucleic acid (RNA) is eligible, even if positive for HCV antibody;

• Other severe acute or chronic medical or psychiatric condition or laboratoryabnormality that may increase the risk associated with study participation orstudy treatment, or may interfere with the interpretation of study results, andin the judgment of the investigator or sub-investigator would make the patientinappropriate for entry into this study;

• Previous or concurrent cancer that is distinct in primary disease or histology fromthe cancer being evaluated in this study, except cervical carcinoma in situ, treatedbasal cell carcinoma, superficial bladder tumors (stage Ta, Tis and T1), cancerscorresponding to intraepithelial or intramucosal neoplasia, or any cancer curativelytreated > 5 years prior to the day on which study treatment is scheduledto be started;

• WOCBP or male patients who do not agree to effective birth control during thefollowing period

1. WOCBP patients: during the clinical study and until 100 days after the lastdose of AB122, 180 days after TAS-116, TAS-102, TAS-120 or TAS-115, whicheveris later;

2. Male patients with WOCBP partners: during the clinical study and until 100 daysafter the last dose of AB122, 180 days after TAS-116, TAS-102, TAS-120 orTAS-115, whichever is later;

• Prior treatment with an anti-PD-L1 anti-PD-1, anti-CTLA-4, or other ICI or agonistas monotherapy or in combination (except for cohort B-3, C-1, D-1 tolerability partand E-1).

• Has received a live vaccine within 30 days prior to study treatment including, butnot limited to the following examples: measles, mumps, rubella, varicella-zoster,yellow fever, and BCG. The inoculation with inactivated vaccines for seasonalinfluenza is allowed.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days prior to enrollment.

• Has an active autoimmune disease that has required systemic treatment in past 2years (ie, with use of disease modifying agents, corticosteroids orimmunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, orphysiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency) is not considered a form of systemic treatment and is allowed.

• Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis. Patients with previously treated brain metastases may participateprovided they are radiologically stable, ie, without evidence of progression for atleast 28 days by repeat imaging (note that the repeat imaging should be performedduring study screening), clinically stable and without requirement of steroidtreatment for at least 14 days prior to enrollment.

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interfere with thepatient's participation for the full duration of the study, or is not inthe best interest of the patient to participate, in the opinion of the treatinginvestigator. (eg, paresis of intestine, intestinal obstruction, unable to receive 5% dextrose in water [DW] in patients with diabetes mellitus, respiratory failure,renal failure, hepatic failure, cerebrovascular disorder, gastrointestinal ulcersthat require transfusion or are hemorrhagic, and wounds/bone fractures associatedwith neovascularization during the healing process, accumulation of pleural within 2weeks prior to enrollment, ascitic, or pericardial fluid requiring drainage)