Phase 2a Study of BAX69 and 5-FU/Leucovorin or Panitumumab Versus Standard of Care in Subjects With Metastatic Colorectal Cancer
Condition: Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: BAX69 + infusional 5-FU/LV; BAX69 + panitumumab; BAX69 + 5-FU/LV; BAX69 + panitumumab; Standard of Care; Standard of Care
Intervention description: Study Part 1: Safety Run-in
Administered weekly as part of a 4 week treatment cycle
Intravenous injection; Study Part 1: Safety Run-in
Administered weekly as part of a 4 week treatment cycle
Intravenous injection; Study Part 2: Administered weekly as part of a 4 week treatment cycle
•Intravenous injection; Study Part 2: Administered weekly as part of a 4 week treatment cycle
•Intravenous injection; Investigator's choice
Dose according to drug label; Investigator's choice
Dose according to drug label
Choice includes panitumumab in KRAS &NRAS wt group only
Intervention MeSH terms: Fluorouracil; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 115.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the safety and tolerability of BAX69 in combination
      with 5-fluorouracil (5-FU)/leucovorin (LV) or panitumumab to determine the recommended phase
      II dose (RP2D) of each combination; and to compare the efficacy between BAX69 in combination
      with 5-FU/LV for subjects with KRAS or NRAS mutated tumor (mt) or panitumumab, for subjects
      with KRAS and NRAS wild type tumor (wt) and standard of care (SoC) per investigator choice as
      third or fourth treatment line in subjects with progressive measurable metastatic colorectal
      cancer (mCRC).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of a signed informed consent

          2. Male and female subjects 18 years of age and older at the time of screening

          3. Subjects who progressed after receiving at least 2, but no more than 3, prior SoC
             treatment lines

          4. Anticipated life expectancy >3 months at the time of screening

          5. Weight between 40 kg and 180 kg

          6. Histologically or cytologically confirmed diagnosis of CRC

          7. Metastatic CRC not amenable to surgical resection

          8. Known KRAS and NRAS mutation status (if unknown status for either of these genes, and
             no archival tissues is available, a fresh tumor biopsy will be made)

          9. At least 1 measurable lesion as defined by RECIST v1.1

         10. ECOG PS of 0-2

         11. Adequate hematological function, defined as:

               1. Platelet count ≥ 100,000/μL

               2. Prothrombin time and activated partial thromboplastin time (aPTT) < 1.5 times the
                  upper limit of normal (ULN)

               3. Absolute neutrophil count (ANC) ≥ 1,000/μL

               4. Hemoglobin ≥ 9 g/dL, without the need for transfusion in the 2 weeks prior to
                  screening

         12. Adequate renal function, defined as serum creatinine ≤ 2.0 times ULN and creatinine
             clearance > 50 mL/min

         13. Adequate liver function, defined as:

               1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)

                  ≤ 2.5 times ULN for subjects without liver metastases, or ≤ 5 times ULN in the
                  presence of liver metastases

               2. Bilirubin ≤ 2.0 times ULN, unless subject has known Gilbert's syndrome

         14. Adequate venous access

         15. For female subjects of childbearing potential, the subject presents with a negative
             serum pregnancy test at screening and agrees to employ 2 forms of adequate birth
             control measures, including at least 1 barrier method (eg, diaphragm with spermicidal
             jelly or foam, or [for male partner] condom) throughout the course of the study and
             for at least 90 days after the last administration of BAX69. Other acceptable
             contraceptive measures include birth control pills/patches or intrauterine devices

         16. For male subjects, the subject must agree to use adequate contraceptive measures
             including at least 1 barrier method (eg, condom with spermicidal jelly or foam and
             [for the female partner] diaphragm with spermicidal jelly or foam, birth control
             pills/patches, or intrauterine device) and abstain from sperm donation throughout the
             course of the study and for at least 90 days after the last administration of BAX69

         17. Subject is willing and able to comply with the requirements of the protocol.

        Exclusion Criteria:

          1. Known central nervous system metastases

          2. Prior malignancy(s) within the past 3 years, with the exception of curatively treated
             basal or squamous cell carcinoma of the skin, locally advanced prostate cancer, ductal
             carcinoma in situ of breast, in situ cervical carcinoma and superficial bladder cancer

          3. Prior treatment with panitumumab for subjects with KRAS and NRAS wt tumor

          4. Residual AE from previous treatment > Grade 1

          5. Prior intolerance to fluoropyrimidine for subjects with KRAS or NRAS mut tumor

          6. Myocardial infarction within 6 months prior to C1D1, and/or prior diagnoses of
             congestive heart failure (New York Heart Association Class III or IV), unstable
             angina, unstable cardiac arrhythmia requiring medication; and/or the subject is at
             risk for polymorphic ventricular tachycardia (eg, hypokalemia, family history or long
             QT syndrome)

          7. Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or
             diastolic blood pressure ≥ 100 mmHg confirmed upon repeated measures

          8. LVEF < 40% as determined by echocardiogram performed at screening or within 90 days
             prior to C1D1

          9. QT/QTc interval > 450 msec, as determined by screening ECG performed no earlier than 1
             week before C1D1

         10. Prior anti-tumor therapy (chemotherapy, radiotherapy, antibody therapy, molecular
             targeted therapy, retinoid therapy or hormonal therapy) within 4 weeks prior to C1D1.

         11. Major surgery within 4 weeks prior to C1D1

         12. Active joint inflammation or history of inflammatory arthritis or other immune
             disorder involving joints

         13. Active infection involving IV antibiotics within 2 weeks prior to C1D1

         14. Known history of, or active hepatitis B virus (HBV), hepatitis C virus (HCV) or active
             tuberculosis

         15. Known history of human immunodeficiency virus (HIV) type 1/2 or other immunodeficiency
             disease

         16. Subject has received a live vaccine within 4 weeks prior to C1D1

         17. Known hypersensitivity to any component of recombinant protein production by CHO cells

         18. Exposure to an investigational product or investigational device in another clinical
             study within 4 weeks prior to C1D1, or is scheduled to participate in another clinical
             study involving an investigational product or device during the course of this study

         19. Subject is nursing or intends to begin nursing during the course of the study

         20. Any disorder or disease, or clinically significant abnormality on laboratory or other
             clinical test(s) (eg, blood tests, ECG), that in medical judgment of the investigator
             may impede the subject's participation in the study, pose increased risk to the
             subject, and/or confound the results of the study

         21. Subject is a family member or employee of the investigator