Botensilimab and Balstilimab Optimization in Colorectal Cancer

ABSTRACT

ConditionColorectal Cancer

InterventionDrug Botensilimab;Drug Balstilimab;Drug Oxaliplatin;Drug Leucovorin;Drug Fluorouracil;Drug Bevacizumab;Drug Panitumumab

Primary outcome:Disease control rate based on iRECIST at second restaging scan;Proportion of subjects with a best overall response of complete response or partial response according to iRECIST

Criteria
Inclusion Criteria

1. Male or female participants who are at least 18 years of age on the day of signing
informed consent.

2. Histologically confirmed metastatic and/or unresectable colorectal cancer without
liver metastasis or known or suspected bone or brain metastases.

a. Up to 3 patients with peritoneal carcinomatosis will be included. Other than those
three, subjects must only have lung, lymph node, and locoregional sites of disease
(primary tumor or serosal implant without carcinomatosis).

3. Microsatellite stable disease.

4. Subject must be willing to provide fresh biopsy of tumor lesion. Those who do not have
a tumor lesion that is safe and amenable to biopsy may still be enrolled.

5. ECOG performance status of 0 or 1.

6. No prior systemic therapy for colon cancer.

a. Subjects who received systemic therapy in the neoadjuvant or adjuvant setting may
be eligible with approval from the principal investigator.

7. Measurable disease per RECIST v1.1.

8. Female participants must not be pregnant or breastfeeding and meet at least one of the
following conditions

1. Not a woman of childbearing potential (WOCBP).

2. A WOCBP must agree to use a reliable method of contraception during the treatment
period and for at least 180 days after the last dose of study treatment.

9. Male participants must practice effective contraceptive methods during the treatment
period, unless documentation of infertility exists.

10. Expected to survive >3 months per investigator assessment.

11. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.

12. Adequate organ function as defined below. Specimens must have been collected within 7
days prior to the start of study treatment

- Absolute neutrophil count (ANC) =1500/µL

- Platelets =100,000/µL

- Hemoglobin =9.0 g/dL or =5.6 mmol/L (without packed red blood cell transfusion
within the last 2 weeks)

- Creatinine OR measured or calculated creatinine clearance (GFR can be used in
place of CrCl) =1.5 x ULN OR =45 mL/min for participant with creatinine levels
>1.5 x institutional ULN (Creatinine clearance should be calculated per
institutional standard.)

- Total bilirubin =1.5 x ULN OR direct bilirubin =ULN for participants with total
bilirubin levels > 1.5 x ULN

- AST (SGOT) and ALT (SGPT) =2.5 x ULN

- International normalized ratio (INR) OR prothrombin time (PT) =1.5 x ULN unless
participant is receiving anticoagulant therapy as long as PT or aPTT is within
therapeutic range of intended use of anticoagulants

- Activated partial thromboplastin time (aPTT) =1.5 x ULN unless participant is
receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range
of intended use of anticoagulants

Exclusion Criteria

1. Prior therapy with an immune checkpoint inhibitor.

2. A WOCBP who is pregnant or breastfeeding or has a positive pregnancy test within 72
hours prior to receiving study treatment.

3. Not willing to use an effective method of birth control as defined in the protocol.

4. Known liver, bone, or CNS metastases and/or carcinomatous meningitis.

5. Diagnosis of other carcinomas within the last 2 years, except cured non-melanoma skin
cancer, treated thyroid cancer, curatively treated in-situ cervical cancer, or
localized prostate cancer treated curatively with no evidence of biochemical or
imaging recurrence.

6. Documented history of clinically significant autoimmune disease or syndrome that
requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, type 1
diabetes mellitus, psoriasis not requiring systemic treatment, well-controlled
hypothyroidism, or conditions not expected to recur in the absence of an external
trigger are permitted to enroll.

7. Any history of chronic or autoimmune pancreatitis.

8. Known history of or any evidence of active, non-infectious pneumonitis.

9. Current use of medications specified by the protocol as prohibited for administration
in combination with study drug.

1. Patients with a condition requiring systemic treatment with either
corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive
medications within 14 days prior to the start of study drug are not eligible.

2. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily
prednisone equivalents are permitted in the absence of active autoimmune disease.

3. Corticosteroids administered as pre-medication for IV contrast allergy are also
allowed.

10. Received a live vaccine within 30 days prior to the start of study drug.

1. Seasonal influenza vaccines for injection are generally killed virus vaccines and
are allowed. However, intranasal influenza vaccines (e.g. Flu-Mist) are
live-attenuated vaccines, and are not allowed within 28 days of study treatment.

2. COVID-19 vaccines will be allowed. However, COVID-19 vaccines are not allowed
within 7 days of starting study drug treatment.

11. Recent or current active infectious disease requiring systemic antivirals,
antibiotics, or antifungals, or treatment within 2 weeks prior to the start of study
drug.

12. Concurrent severe and/or uncontrolled medical conditions, which may compromise
participation in the study, including impaired heart function or clinically
significant heart disease.

13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to the start of study drug (56 days for hepatectomy, open thoracotomy, major
neurosurgery) or anticipation of need for major surgical procedure during the course
of the study.

14. Serious, non-healing wound, ulcer, or bone fracture.

15. Patients with a history of organ or allogenic hematopoietic stem cell transplantation.

16. Partial or complete bowel obstruction within the last 3 months, signs/ symptoms of
bowel obstruction, or known radiologic evidence of impeding obstruction.

17. Refractory ascites defined as requiring 2 or more therapeutic paracenteses within the
last 4 weeks or =4 times within the last 90 days or =1 time within the last 2 weeks
prior to study entry or requiring diuretics within 2 weeks of study entry.

18. Positive tuberculosis test at screening.