This is a Phase 1/1b, open-label, dose-escalation, and dose-expansion study to evaluate the
safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of
etrumadenant (AB928) in combination with mFOLFOX in participants with advanced metastatic
gastroesophageal Cancer (GEC) or colorectal cancer (CRC).
In the dose escalation phase, escalating doses of etrumadenant in combination with mFOLFOX at
standard doses will be assessed in participants with advanced metastatic GEC or CRC. Eligible
participants will receive oral administration of etrumadenant as well as IV infusion of
mFOLFOX. The recommended dose for expansion (RDE) of etrumadenant will be determined upon
completion of the dose-escalation phase.
In the dose expansion phase, etrumadenant at the RDE in combination with mFOLFOX at standard
doses may be assessed in participants with advanced metastatic GEC or CRC.
Overall duration of treatment will depend on how well the treatment is tolerated. Treatment
may continue until unacceptable toxicity or progressive disease or other reasons specified in
the protocol.
Inclusion Criteria:
1. Male or female participants ≥ 18 years
2. Histologically confirmed gastroesophageal cancer or colorectal cancer that is
metastatic, advanced or recurrent with progression
3. Participants for whom mFOLFOX is considered appropriate therapy
4. Must have at least 1 measurable lesion per RECIST v1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
6. Must have received standard of care, including potentially curative available
therapies or interventions.
7. Confirm that an archival tissue sample is available and ≤ 24 months old; if not, a new
biopsy of a tumor lesion must be obtained.
8. Adequate organ and marrow function
Exclusion Criteria:
1. Use of any live vaccines against infectious diseases (eg, influenza, varicella) within
4 weeks (28 days) of initiation of investigational product.
2. Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will
make the administration of investigational product 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.
3. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
4. Untreated or symptomatic CNS disease
5. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with screening visit through 30 days after
the last dose of etrumadenant in combination with mFOLFOX.
6. Any active autoimmune disease or a documented history of autoimmune disease or
syndrome that required systemic treatment in past 2 years (ie, with use of
disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for
vitiligo or resolved childhood asthma/atopy.
1. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a
form of systemic treatment.
2. 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.
8. Oxaliplatin-based therapy as the most recent regimen prior to enrolling in the study,
except if prior oxaliplatin-based therapy was received as the most recent regimen in
the adjuvant setting and completed ≥ 6 months prior to study enrollment.
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. Use of other investigational drugs (drugs not marketed for any indication) within 28
days of investigational product administration.
