SGNTUC-029 - MOUNTAINEER-03 (JCP127)

An Open-label Randomized Phase 3 Study of Tucatinib in Combination with Trastuzumab and mFOLFOX6 versus mFOLFOX6 given with or without either Cetuximab or Bevacizumab as First-line Treatment for Subjects with HER2+ Metastatic Colorectal Cancer

---

Population: mCRC HER2+

Line of therapy: 1L

Intervention: Screening for HER2, RAS (central testing) Tucatinib (PO BID) + trastuzumab q3w + mFOLFOX6 q2w vs. SOC (mFOLFOX6 q2w +/-either bevacizumab q2w or cetuximab q1w, investigator`s choice)

Key Inclusion Criteria

1. histologically and/or cytologically documented adenocarcinoma of the colon or rectum, which is metastatic and/or unresectable

2. provide the most recently available formalin-fixed paraffin-embedded tumor tissue blocks (or freshly sectioned slides), obtained prior to treatment initiation. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to the Cycle 1 Day 1 timeframe. Biopsy must provide adequate tissue for analysis; the following biopsy types are acceptable: resection, excision, punch (skin lesions only) and core needle biopsies.

3. HER2+ disease as determined by tissue-based investigational HER2 IHC and ISH assays performed at central laboratory (using ASCO/CAP guidelines for gastric and gastroesophageal cancer with IHC 3+ or IHC 2+/ISH+ result).

4. RAS WT disease as determined by local or central testing

5. radiographically measurable disease per RECIST v1.1, with at least one site of disease that is measurable and that has not been previously irradiated; or, if the subject has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation

6. ECOG 0 or 1

7. Life expectancy of ≥3 months

8. Have adequate hematological, hepatic, renal, coagulation, and cardiac function, obtained ≤7 days prior to enrollment (Cycle 1 Day 1):

9. LVEF ≥50% as assessed by ECHO or MUGA documented ≤28 days prior to study treatment

10. Subject must be willing and able to adhere to mandatory antidiarrheal prophylaxis.

11. See protocol for CNS inclusion details

    
    

Key Exclusion Criteria

1. Any systemic anticancer tx for CRC in the metastatic setting or have participated in any interventional clinical trial for CRC in the metastatic setting. Subjects may have received prior chemotx for CRC in the adjuvant setting if completed >6 months prior to enrollment.

2. Radiation therapy < 14 days prior to enrollment

3. Previous anti-HER2 therapy

4. Toxicity related to prior cancer therapies not resolved to ≤ Grade 1, with exceptions in protocol

5. Clinically significant cardiopulmonary disease

6. Hx of transient ischemic attack, cerebrovascular accident, MI, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac sx < 6 months prior to enrollment

7. Hx of a significant bleeding events < 6 months of enrollment, unless definitively treated; hx of GI perforation < 12 months of enrollment

8. Ongoing ≥ Grade 2 diarrhea of any etiology at screening

9. Major sx or significant traumatic injury ≤28 days prior to enrollment (≤56 days for hepatectomy, open thoracotomy, or major neurosx) or anticipation of need for major sx during the course of the study

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

11. Positive for hepB by surface antigen expression or presence of known chronic liver disease; active hepC infection (positive by PCR or on antiviral tx for hepC <6 months); positive for HIV (exceptions in protocol)

12. Used strong p450 (CYP) 2C8 inhibitor < 5 half-lives of the inhibitor, or have used a strong CYP2C8 or CYP3A4 inducer < 5 days prior to study tx

13. Another malignancy <3 years (exceptions in protocol)

14. Active CNS metastases

15. Dihydropyrimidine dehydrogenase (DPD) deficiency

Sponsor: Seagen Inc.

CRP Contact: rhythm.sharma@ladydavis.ca

CRP PI: Dr. P. Kavan

Status: Open to accrual