Evaluating the safety of AB122 in patients with advanced solid tumors

Inclusion Criteria:

* Is male or female aged ≥ 18 years at the time of informed consent; Willing and able to 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 1 before 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, AST and 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 of granulocyte colony-stimulating factor \[G-CSF\])
  * Platelet count ≥ 100000 /mm3 (SI: ≥ 100 × 109 /L) (excluding measurements obtained within 7 days after a transfusion of platelets)
  * Hemoglobin value of ≥ 9.0 g/dL excluding measurements within 4 weeks after a transfusion 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 for advanced 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 metastatic disease, 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 or metastatic disease, and was refractory or intolerant to the standard treatment
* Has been most recently received regimen including an ICI (anti PD-1 antibodies, anti PD-L1 antibodies or anti CTLA-4 antibodies) and platinum-based chemotherapy in combination or in sequence (i.e., platinum-based chemotherapy followed by checkpoint inhibitor 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 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 the mid-pharynx.

  • Patient background such as combined positive score (CPS) and head and neck cancer treatment guidelines must be taken into account to confirm the validity of enrollment in this cohort.
* 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. • Treatment of locally advanced disease completed more than 6 months prior to the start of study drug administration is not considered prior therapy.

Cohort D-5

* Has histologically or cytologically confirmed recurrent or advanced squamous head and 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 guidelines must be taken into account to confirm the validity of enrollment in this cohort.
* 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. • Treatment of locally advanced disease completed more than 6 months prior to the start of study drug administration is 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 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-7

* Has histologically confirmed unresectable or advanced biliary tract cancer (intrahepatic bile duct, extrahepatic bile duct, gallbladder, or duodenal papillary region) with a diagnosis of adenocarcinoma or adenosquamous carcinoma.
* 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-8

* Has histologically confirmed unresectable or advanced pancreatic ductal adenocarcinoma (highly differentiated, moderately differentiated, or poorly differentiated).
* 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-9 - 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 the mid-pharynx.

Patient background such as combined positive score (CPS) and head and neck cancer treatment guidelines must be taken into account to confirm the validity of enrollment in this cohort.

\- 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.

Treatment of locally advanced disease completed more than 6 months prior to the start of study drug administration is not considered prior therapy.

Cohort E-1

* Has a histologically or cytologically 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 (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-1 antibodies, anti PD-L1 antibodies or anti CTLA-4 antibodies), and all of the following 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 able to comply with scheduled visits and study procedure

Exclusion Criteria:

* Clinically significant history or current evidence of cardiac arrhythmia and/or conduction abnormality: Any factor that can increase the risk of corrected QT interval (QTc) prolongation or risk 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 day on which study treatment is scheduled to be started:

  * Major surgery within 4 weeks (the surgical incision should be fully healed prior 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 (excluding anemia, peripheral sensory neuropathy, alopecia and skin pigmentation);
* A serious illness or medical condition(s) including, but not limited to, the following specific medical conditions:

  * Known acute systemic infection;
  * Known medical history of interstitial lung disease/ drug-induced interstitial lung disease/ radiation pneumonitis which required steroid treatment/ any evidence of clinically active interstitial lung disease;
  * Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV, Appendix A) within the previous 6 months; if \> 6 months, cardiac function must be within 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 B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody in baseline virus test. 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 laboratory abnormality that may increase the risk associated with study participation or study treatment, or may interfere with the interpretation of study results, and in the judgment of the investigator or sub-investigator would make the patient inappropriate for entry into this study;
* Previous or concurrent cancer that is distinct in primary disease or histology from the cancer being evaluated in this study, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (stage Ta, Tis and T1), cancers corresponding to intraepithelial or intramucosal neoplasia, or any cancer curatively treated \> 5 years prior to the day on which study treatment is scheduled to be started;
* WOCBP or male patients who do not agree to effective birth control during the following period

  1. WOCBP patients: during the clinical study and until 100 days after the last dose of AB122, 180 days after TAS-116, TAS-102, TAS-120 or TAS-115, whichever is later;
  2. Male patients with WOCBP partners: during the clinical study and until 100 days after the last dose of AB122, 180 days after TAS-116, TAS-102, TAS-120 or TAS-115, whichever is later;
* Prior treatment with an anti-PD-L1 anti-PD-1, anti-CTLA-4, or other ICI or agonist as monotherapy or in combination (except for cohort B-3, C-1, D-1 tolerability part and E-1).
* Has received a live vaccine within 30 days prior to study treatment including, but not limited to the following examples: measles, mumps, rubella, varicella-zoster, yellow fever, and BCG. The inoculation with inactivated vaccines for seasonal influenza 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 of immunosuppressive therapy within 7 days prior to enrollment.
* Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 28 days by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to enrollment.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient\'s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator. (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 ulcers that require transfusion or are hemorrhagic, and wounds/bone fractures associated with neovascularization during the healing process, accumulation of pleural within 2 weeks prior to enrollment, ascitic, or pericardial fluid requiring drainage)