- Willing and able to provide written informed consent for the trial.
- Be ≥18 years of age on the date of signing informed consent.
- ECOG performance status of 0 or 1.
- Histologically confirmed rectal adenocarcinoma.
- Clinical stage: Stage II (T3-4, N-) or Stage III (any T, N+)
- No evidence of distant metastases.
- Radiologically measurable or clinically evaluable disease
- Tumor specimen that demonstrates mismatch repair deficiency by Immunohistochemistry or
microsatellite instability as demonstrated by NGS or PCR.
- Negative pregnancy test done 72 hours prior to registration, for women of childbearing
potential only. Subjects of childbearing potential must be willing to use an adequate
method of contraception. Appropriate methods of birth control include abstinence, oral
contraceptives, implantable hormonal contraceptives, or double barrier method
(diaphragm plus condom). Contraception, for the course of the study starting with the
first dose of study medication through 150 days after the last dose of study
medication. Note: Abstinence is acceptable if this is the usual lifestyle and
preferred contraception for the subject.
Nonchildbearing potential is defined as follows (by other than medical reasons):
- ≥45 years of age and has not had menses for >1 year
- Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and
oophorectomy must have a follicle stimulating hormone value in the postmenopausal
range upon screening evaluation
- Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented
hysterectomy or oophorectomy must be confirmed with medical records of the actual
procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical
records of the actual procedure, otherwise the patient must be willing to use 2
adequate barrier methods throughout the study.
- Participant receiving corticosteroids may continue as long as their dose is
stable for least 4 weeks prior to initiating protocol therapy.
- Demonstrate adequate organ function as defined below, all screening labs should
be performed within 8 days of treatment initiation.
- Recurrent rectal cancer.
- Prior pelvic radiation therapy, chemotherapy, or surgery for rectal cancer.
- Absolute neutrophil count (ANC) ≥1,500 /mcL
- Platelets ≥100,000 / mcL
- Hemoglobin >9 g/dL or ≥5.6 mmol/L
°Serum creatinine OR Measured or calculated(a) creatinine clearance (GFR can also be
used in place of creatinine or CrCl) ≤1.5 × upper limit of normal (ULN) OR ≥60 mL/min
for subject with creatinine levels > 1.5 × institutional ULN
- Serum total bilirubin ≤ 1.5 × ULN OR Direct bilirubin ≤ ULN for subjects with
total bilirubin levels > 1.5 ULN
- AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN
°International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial
Thromboplastin Time (aPTT) ≤1.5 × ULN unless subject is receiving anticoagulant
therapy as long as PT or PTT is within therapeutic range of intended use of
anticoagulants ≤1.5 × ULN unless subject is receiving anticoagulant therapy as long as
PT or PTT is within therapeutic range of intended
(a) Creatinine clearance should be calculated per institutional standard.
- Tumor is causing symptomatic bowel obstruction (patients who have a temporary
diverting ostomy are eligible).
- Other invasive malignancy ≤ 5 years prior to registration. Exceptions are non-melanoma
skin cancer that has undergone potentially curative therapy and in situ cervical
- Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
of non- physiologic dose immunosuppressive therapy within 7 days prior to first dose
of trial treatment.
- Active autoimmune disease requiring systemic treatment within the past 2 years or
documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic steroids or immunosuppressive agents at non-physiologic doses.
- Active infection requiring systemic therapy.
- Received prior therapy with an antibody or drug specifically targeting T- cell
co-stimulation or checkpoint pathways.
- Experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the exception
of non-clinically significant lab abnormalities.
- Other Anticancer or Experimental Therapy. No other experimental therapies (including
chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene
therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors,
thalidomide, anti-VEGF/Flk-1 monoclonal antibody or other experimental drugs) of any
kind are permitted while the patient is receiving study treatment.
- Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
- Women who are pregnant or breastfeeding, or men expecting to conceive or father
children within the projected duration of the trial, starting with the pre-screening
visit through 150 days after the last dose of study medication.
- Concurrent medical or psychiatric condition or disease which, in the investigator's
judgement, would make them inappropriate candidates for entry into the study. Examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within
90 days) myocardial infarction, chronic obstructive pulmonary disease, uncontrolled
major seizure disorder, unstable spinal cord compression, superior vena cava syndrome,
or any psychiatric disorder that prohibits obtaining informed consent.
- Received a live vaccine within 30 days of planned start of study medication.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to enrollment.
- History of interstitial lung disease.
- Known hypersensitivity to TSR-042 components or excipients.