Non squamous cell Non Small Cell Lung Cancer

Primary • To evaluate the safety and tolerability of AB928 combination therapy and AB122 monotherapy in participants with NSCLC Secondary • To describe the immunogenicity of AB122 in participants with NSCLC • To describe the PK profiles of AB928 in each combination therapy and AB122 monotherapy • To assess the potential PD effects of AB928 in each combination therapy and AB122 monotherapy • To determine the clinical activity of AB928 combination therapy and AB122 monotherapy in participants with NSCLC

AB122, AB928

AB122
AB928

IV injection
Capsule

120 mg/ 4mL
25 mg

Primary Outcome Measures :
Percentage of participants with Adverse Events [ Time Frame: From first study treatment administration until up to 90 days after the last dose (Approximately 1 year) ]
Percentage of participants who experience a Dose Limiting Toxicity [ Time Frame: From first study treatment administration through Day 21 ]

Secondary Outcome Measures :
Percentage of participants with anti-drug antibodies to zimberelimab [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months). ]
Plasma concentration of etrumadenant [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months). ]
Serum concentration of zimberelimab [ Time Frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months). ]
Progression Free Survival (PFS) [ Time Frame: From start of treatment up to the first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years) ]
Overall Survival (OS) [ Time Frame: From study start of treatment up to death from any cause (up to approximately 3-5 years) ]
Duration of Response [ Time Frame: From the date of first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years) ]
Percentage of Participants with Disease Control (complete response, partial response, or stable disease) for >6 months [ Time Frame: From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years) ]
Percentage of participants with Objective Response [ Time Frame: From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 3-5 years) ]

1. Male or female participants; age ≥ 18 years at the time of screening.
2. Capable of giving signed informed consent as described in Section 10.4, which includes
compliance with the requirements and restrictions listed in the informed consent form
(ICF) and in this protocol.
3. Women with no childbearing potential because of surgery or who are at least 1 year
postmenopausal (ie, 12 months post last menstrual period) or menopause confirmed by
follicle-stimulating hormone testing.
4. Women of childbearing potential must use an effective nonhormonal method of
contraception (intrauterine device or intrauterine system; condom or occlusive cap
[diaphragm or cervical or vault caps] with spermicidal foam or gel or film or cream or
suppository; or vasectomized male partner if he is the sole partner of that participant) for
the duration of the study and for 30 days after the last dose of investigational product for
non-PD-1-containing regimens and 90 days after the last dose of investigational product
for PD-1-containing regimens.
5. Negative serum pregnancy test at screening and prior to dosing on Cycle 1 Day 1 and a
negative serum or urine pregnancy test on the first day of each subsequent treatment
period (women of childbearing potential only).
6. Male participants must use an effective method of contraception (condom or occlusive
cap [diaphragm or cervical or vault caps] with spermicidal foam or gel or film or cream
or suppository; or vasectomy) throughout the study and 30 days after the last dose of
investigational product for non-PD-1-containing regimens and 90 days after the last dose
of investigational product for PD-1-containing regimens.
7. Disease-specific criteria for Arm A:
a. Pathologically confirmed nonsquamous NSCLC that is metastatic, locally advanced,
or recurrent with progression. Additionally, participants must fulfill one of the
following criteria:
i. No alternative or curative therapy exists. Participants may have received any
number of prior therapies defined by radiographic progressive disease.
ii. Have a genetic alteration (mutation or genetic rearrangement for which a targeted
therapy exists) and failed treatment with ≥ 1 tyrosine kinase inhibitor (TKI) AND
must not have received any chemotherapy or any anti-PD-1/PD-L1-based therapy.
iii. Treatment-naïve participants who refused therapy (documented in the medical
record) OR are considered appropriate candidates for study treatment by the
Principal Investigator. Recurrent disease occurring ≥ 6 months after receiving
adjuvant or neoadjuvant therapy in the locally advanced setting is defined as
treatment naïve if no other therapy has been received between
neoadjuvant/adjuvant therapy and screening.
iv. Naïve to a platinum-based therapy but progressed on anti-PD-1/PD-L1-based
therapy (as monotherapy or combination therapy). If primary refractory to
anti-PD-1/PD-L1-based therapy (disease progression occurring ≤ 16 weeks after
the start of the anti-PD-1/PD-L1-based therapy), no intervening therapy must
have been received between the anti-PD-1/PD-L1-based therapy and screening.
v. Progressed on anti-PD-1/PD-L1-based therapy (as monotherapy or combination
therapy) but received < 4 cycles of carboplatin/pemetrexed and further platinumbased therapy is considered appropriate.
8. Disease-specific criteria for Arm B:
a. Pathologically confirmed nonsquamous NSCLC that is metastatic, locally advanced,
or recurrent with progression. Additionally, participants must fulfill one of the
following criteria:
i. No alternative or curative therapy exists. Participants may have received any
number of prior therapies defined by radiographic progressive disease.
ii. Have a genetic alteration (mutation or genetic rearrangement for which a targeted
therapy exists) and failed treatment with ≥ 1 TKI and must not have received any
chemotherapy or any anti-PD-1/PD-L1-based therapy.
iii. Treatment-naïve participants who refused therapy (documented in the medical
record) OR are considered appropriate candidates for study treatment by the
Principal Investigator. Recurrent disease occurring ≥ 6 months after receiving
adjuvant or neoadjuvant therapy in the locally advanced setting is defined as
treatment naïve if no other therapy has been received between
neoadjuvant/adjuvant therapy and screening.
9. Disease-specific criteria for Arm 1 and Arm 2:
a. Pathologically confirmed nonsquamous NSCLC that is metastatic, locally advanced,
or recurrent with progression.
b. Have a genetic alteration (mutation or genetic rearrangement for which a targeted
therapy exists) and failed treatment with ≥ 1 TKI and must not have received any
chemotherapy or any anti-PD-1/PD-L1-based therapy.
10. Disease-specific criteria for Arm 3:
a. Pathologically confirmed nonsquamous NSCLC that is metastatic, advanced, or
recurrent with progression. Subjects must be treatment-naïve in these settings and
have ≥ 50% tumoral PD-L1 expression tested by the DAKO assay.
11. Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors
(RECIST v1.1).
12. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 (see
Appendix 2).
13. Archival tissue sample
a. For Arm A and Arm B: Confirm that an archival tissue sample is available and
≤ 6 months old; if not, a new biopsy of a tumor lesion not previously irradiated
(tumors progressing in a prior site of radiation may be considered after Sponsor
consultation) should be obtained. However, the biopsy must not put participants at
undue risk, and the procedure must not be more invasive than a core biopsy as
documented in the medical record by the Investigator.
b. For Arm 1, Arm 2, and Arm 3: Confirm that an archival tissue sample is ≤ 6 months
old and shipped. If not, a new biopsy of a tumor lesion not previously irradiated
(tumors progressing in a prior site of radiation may be considered after Sponsor
consultation) should be obtained. However, the biopsy must not put participants at
undue risk and the procedure must not be more invasive than a core biopsy. If the
biopsy cannot be safely obtained, then the participant is not eligible.
14. Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given
to control the cancer) or biologic agents must have been completed at least 4 weeks
before investigational product administration, and all AEs have either returned to baseline
or stabilized.
15. Previously treated central nervous system (CNS) metastases, meeting the following
criteria:
a. No evidence of progression by magnetic resonance imaging (MRI) for at least
4 weeks prior to first dose.
b. Neurologic symptoms returned to baseline.
c. No immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone or
equivalent) for at least 2 weeks before investigational product administration.
d. No carcinomatous meningitis, which is excluded regardless of clinical stability.
16. Prior radiation therapy must have been completed as follows:
a. Prior systemic radiation or whole brain radiation at least 4 weeks before
investigational product administration.
b. Prior focal radiotherapy at least 2 weeks before investigational product
administration.
c. No radiopharmaceuticals (strontium, samarium) may have been administered.
17. Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed
topical corticosteroids (doses > 10 mg/day prednisone or equivalent) must be
discontinued at least 2 weeks (14 days) before investigational product administration.
Physiologic doses of corticosteroids ≤ 10 mg/day of prednisone or its equivalent may be
permitted.
18. Prior surgery that required general anesthesia must be completed at least 4 weeks before
investigational product administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before investigational product administration.
Participants should have recovered from the surgical procedure. Cutaneous biopsies with
only local anesthesia should be completed at least 1 hour prior to investigational product
administration.
19. Negative tests for hepatitis B surface antigen, hepatitis C virus antibody (or hepatitis C
qualitative ribonucleic acid [RNA]) and human immunodeficiency virus (HIV)-1 and
HIV-2 antibody at screening.
20. Adequate organ and marrow function, as defined below:
a. Neutrophils ≥ 1500/μL
b. Platelets ≥ 100 x 103
/μL
c. Hemoglobin ≥ 9.0 g/dL
d. Creatinine clearance ≥ 45 mL/min as determined by Cockcroft-Gault equation
(Cockcroft and Gault, 1976) or by 24-hour urine collection for determination of
creatinine clearance
e. Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) without
hepatic metastasis and ≤ 5 x ULN with hepatic metastasis
f. Alanine aminotransferase (ALT) ≤ 2.5 x ULN without hepatic metastasis and
≤ 5 x ULN with hepatic metastasis
g. Bilirubin ≤ 2 x ULN (except participants with Gilbert’s syndrome who must have
total bilirubin < 3.0 mg/dL).

1. Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation
of investigational product(s).
2. Any acute gastrointestinal symptoms (eg, nausea, vomiting, diarrhea, heartburn) at the
time of screening or admission.
3. Underlying medical conditions that, in the Investigator’s or Sponsor’s opinion, will make
the administration of investigational product(s) hazardous (eg, interstitial lung disease,
active infections requiring antibiotics, recent hospitalization with unresolved symptoms)
or obscure the interpretation of toxicity determination or AEs, or concurrent medical
condition requiring the use of immunosuppressive medications or immunosuppressive
doses of systemic or absorbable topical corticosteroids.
4. Has known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial.
5. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the pre-screening or screening visit through
30 days after the last dose of investigational product for non-PD-1-containing regimens
and through 90 days after the last dose of investigational products for PD-1-containing
regimens.
Cancer-specific Exclusion Criteria
6. Any active autoimmune disease or a documented history of autoimmune disease or
syndrome that required systemic treatment in the past 2 years (ie, with use of diseasemodifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or
resolved childhood asthma/atopy.
a. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form of
systemic treatment.
b. Participants with asthma who require intermittent use of bronchodilators, inhaled
corticosteroids, or local corticosteroid injections will not be excluded from this study.
Participants on chronic systemic corticosteroids will be excluded from the study.
7. Prior malignancy active within the previous 2 years except for locally curable cancers
that have been apparently cured, such as basal or squamous cell skin cancer, superficial
bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer.
Treatment-specific Exclusion Criteria
8. For Arm 3 only: Prior treatment with an anti-PD-L1, anti-PD-1, anti-CTLA-4, or other
immune checkpoint inhibitor or agonist as monotherapy or in combination.
9. Prior chemotherapy, targeted small-molecule therapy, or radiation therapy within 4 weeks
prior to Day 1 or has not recovered (ie, ≤ Grade 1 or baseline) from AEs due to a
previously administered agent, except ≤ Grade 2 alopecia or ≤ Grade 2 neuropathy and
other AEs considered not clinically significant by the Medical Monitor and Investigator.
10. For all arms, except Arm 3: Participants who received prior anti-PD-1/PD-L1-based
therapy and experienced any of the following:
a. Any Grade 1 to 4 immune-related AEs that did not improve to ≤ Grade 1 or baseline
using current National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Events (CTCAE 5.0) and received steroid therapy and/or other
immunosuppressive therapy, as treatment for immune-related AEs, within 30 days of
study entry.
b. Any Grade 1 to 4 ocular or neurologic events that did not improve to ≤ Grade 1 or
baseline and received steroid therapy and/or other immunosuppressive therapy, as
treatment for immune-related AEs, within 30 days of study entry.
11. Prior use of an adenosine pathway targeting agent.
12. Participants who are eligible for potentially curative available therapies or interventions.
13. Use of other investigational drugs (drugs not marketed for any indication) within 28 days
or at least 5 half-lives (whichever is longer) before investigational product administration.