AB122 Platform study

JRCT ID: jRCT2011210020

Registered date:27/07/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced or metastatic solid tumor
• Date of first enrollment: 06/09/2021
• Target sample size: 367
• Study type: Interventional

Intervention(s)

Phase 1a
- Cohort A-1: AB122 will be administered with 240 mg/body given by infusion over 60 minutes Q2W.
- Cohort A-2: AB122 will be administered with 360 mg/body given by infusion over 60 minutes Q3W.
- Cohort B-n: AB122 will be administered with 240 mg/body given by infusion over 60 minutes Q2W. TAS-116 will be administered orally in 5-day on and 2-day off schedule on an empty stomach at least 1 hour before or 2 hour after eating.
- Cohort D-1: AB122 will be administered with 360 mg/body given by infusion over 60 minutes every 3 weeks. TAS-120 will be administered orally once daily (QD) on an empty stomach at least 1 hour before or 2 hours after eating.
- Cohort E-n: AB122 will be administered with 360 mg/body given by infusion over 60 minutes every 3 weeks. TAS-115 will be administered orally in 5-day on and 2-day off schedule on an empty stomach at least 1 hour before or 2 hours after eating.

Phase 1b
The dose level will be determined based on tolerability of each cohort in the Phase 1a.

Outcome(s)

Primary Outcome

Phase 1a (general)
- DLTs during Cycle 1
Phase 1b (Cohort B-n, D-1 and E-n)
- ORR by RECIST v1.1

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

General Inclusion Criteria
(1) 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);
(2) Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 before administration of study treatment;
(3) Has adequate organ function as defined by the following criteria:
a.AST and ALT =< 3 x ULN; or if a patient with documented liver metastases, AST and ALT =< 5 x ULN
b.T-Bil of =< 1.5 x ULN
c.ANC >= 1500 /mm3 (ie, >= 1.5 x 109 /L by International System of Units [SI]) (excluding measurements obtained within 7 days after administration of granulocyte colony-stimulating factor [G-CSF])
d.Platelet count >= 100000 /mm3 (SI: >= 100 x 109 /L) (excluding measurements obtained within 7 days after a transfusion of platelets)
e.Hemoglobin value of >= 9.0 g/dL excluding measurements within 4 weeks after a transfusion of packed red blood cells (RBCs) or whole blood
(4) Has a life expectancy of at least 90 days;

Cohort A-1 and A-2
1. Japanese male and female;
2. Has a histologically or cytologically confirmed diagnosis of solid tumor;
3. Has disease progression after standard treatment for advanced or metastatic disease, are intolerant to the standard treatment;

Cohort B-1
1. Has a histologically or cytologically confirmed diagnosis of PDAC;
2. Has disease progression after or intolerant to one prior systemic chemotherapy for advanced or metastatic disease

Cohort B-2
1. Has a histologically or cytologically confirmed diagnosis of CRC.
2. Has been received one regimen of standard chemotherapy for advanced or metastatic disease, and was refractory or intolerant to those chemotherapies

Cohort B-3
1. Has a histologically or cytologically confirmed non-squamous NSCLC;
2. Has been received one or two regimen of standard chemotherapy for advanced or metastatic disease, and was refractory or intolerant to the standard treatment
3. 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);
- At least 2 doses of the ICI therapy
- Radiographic complete response or partial response based on investigator assessment
- Documented radiographic disease progression with above most recently received regimen
4. Has no known actionable genomic alterations in EGFR gene mutation, ALK fusion gene, ROS1 fusion gene, BRAF gene mutation, MET exon 14 skipping, NTRK fusion gene, RET fusion gene, or KRAS gene mutation.(Overexpression of any of the above, in the absence of activating mutations, is not sufficient for enrollment);

Cohort D-1
1.Has histologically confirmed advanced or metastatic NSCLC regardless of histologic type.
2.Has PD-L1 (>= 50% tumor proportion score) in tumor tissue sample as determined at a local laboratory.
3.Has no known actionable genomic alterations in EGFR gene mutation, ALK fusion gene, ROS1 fusion gene, BRAF gene mutation, MET exon 14 skipping, NTRK fusion gene, RET fusion gene, or KRAS gene mutation (overexpression of any of the above, in the absence of activating mutations, is sufficient for enrollment).

Cohort E-1
1. Has a histologically or cytologically confirmed advanced or metastatic NSCLC regardless of histologic type.
2. Has PD-L1 (>= 50% tumor proportion score) in tumor tissue sample as determined at a local laboratory (except for tolerability part).
3. Has been received 1-4 regimen for advanced or metastatic disease
4. Has been received one regimen of ICI monotherapy or combination therapy (anti PD-1 antibodies, anti PD-L1 antibodies or anti CTLA-4 antibodies).
a. At least 2 doses of the ICI therapy
b. Documented radiographic disease progression with or after ICI therapy
5. Has no known actionable genomic alterations in EGFR gene mutation, ALK fusion gene, ROS1 fusion gene, BRAF gene mutation, MET exon 14 skipping, NTRK fusion gene, RET fusion gene, or KRAS gene mutation.(Overexpression of any of the above, in the absence of activating mutations, is sufficient for enrollment);

Cohort E-2
1. Has a histologically or cytologically confirmed advanced or metastatic ASPS
2. Is male or female aged >= 16 years at the time of informed consent; Willing and able to comply with scheduled visits and study procedure

Exclude criteria

(1) 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.;
(2) Treatment with any of the following within the specified time frame prior to the day on which study treatment is scheduled to be started:
a. 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);
b. Extended-field radiotherapy within 4 weeks or limited-field radiotherapy within 2 weeks;
c. Any anticancer therapy within 2 weeks;
d. Any investigational agent received within 5 half-lives of the drug or 4 weeks, whichever shorter;
(3) Unresolved toxicity of >= Grade 2 attributed to any prior therapies (excluding anemia, peripheral sensory neuropathy, alopecia and skin pigmentation);
(4) A serious illness or medical condition(s) including, but not limited to, the following specific medical conditions:
a. Known acute systemic infection;
b. 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;
c. 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;
d. Known severe chronic kidney disease;
e. 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;
f. 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;
(5) 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;
(6) WOCBP or male patients who do not agree to effective birth control during the following period
- WOCBP patients: during the clinical study and until 100 days after the last dose of AB122, 180 days after TAS-116, TAS-120 or TAS-115, whichever is later;
- 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-120 or TAS-115, whichever is later;
(7) 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 cohortB-3, D-1 tolerability part and E-1).
(8) 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.
(9) 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.
(10)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.
(11)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.
(12)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).

Related Information

• Primary Sponsor: Nasermoaddeli Ali