CompassHER2 (MAC.27)

The CompassHER2 Trials (COMprehensive Use of Pathologic Response ASSessment to Optimize Therapy in HER2-Positive Breast Cancer): CompassHER2 Residual Disease (RD), A Double-Blinded, Phase III Randomized Trial of T-DM1 and Placebo Compared with T-DM1 and Tucatinib

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Population: HER2-positive Breast Cancer

Line of therapy: 1L (after induction therapy in participants with previously untreated HER2-positive advanced breast cancer (ABC))

Intervention: T-DM1 and Tucatinib/placebo x 14 cycles

Key Inclusion Criteria

1. HER2-positive breast cancer; ECOG Performance Status 0-1

2. Patients must have received neoadjuvant chemotherapy with one of the following regimens: THP, TMP, AC-TH(P); TCH(P); FAC-TH(P), or FEC-TH(P).

3. Prior receipt of T-DM1 in the neoadjuvant setting is not allowed.

4. Prior treatment must have consisted ≥ 6 cycles of chemotherapy and HER2-directed therapy, with a total duration of ≥ 12 weeks, including at least 9 weeks of preoperative taxane and trastuzumab with or without pertuzumab (or FDA-approved biosimilars). Patients who have received at least 9 weeks of preoperative taxane, pertuzumab and margetuximab are also eligible if they received ≥ 6 cycles of chemotherapy prior to registration.

5. Patients who received neoadjuvant systemic therapy which included experimental HER2-directed therapy are potentially eligible, as long as the investigational agent was not a HER2-targeted antibody-drug conjugate (e.g. T-DM1 or trastuzumab deruxtecan) or a HER2 targeted tyrosine kinase inhibitor (TKI) (e.g. tucatinib, lapatinib, neratinib).

6. Patients may have received ≤ 1 cycle of T-DM1 in the adjuvant setting.

7. Both of the following points must be true: 1) -An interval of no more than 12 weeks between the completion date of the last definitive treatment and the date of registration AND 2)Patients must be registered on study within ≤ 180 days of the date of the most recent definitive breast cancer surgery (not including reconstructive surgery).

8. All systemic chemotherapy should have been completed preoperatively unless participating in EA1181 (CompassHER2 pCR) or the BIG DECRESCENDO Trial (which is very similar to EA1181 in terms of the study design, drugs, and eligibility criteria).

9. Toxicities related to prior systemic treatment should have resolved or be at baseline, apart from alopecia and peripheral neuropathy ≤ grade 1.

10. Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes (see Section 3.2.2)

    
    

Key Exclusion Criteria

1. Adjuvant treatment with any anti-cancer investigational drug within 28 days prior to registration

2. Patients with known active and/or untreated Hepatitis B or Hepatitis C or chronic liver disease are ineligible. Patients with a diagnosis of Hepatitis B or C that has been treated and cleared and normal liver function are eligible to participate in the study if the other eligibility parameters are met.

3. Stage IV (metastatic) breast cancer

4. History of any prior (ipsi- or contralateral) invasive breast cancer within 3 years of registration

5. Patients with ER+ HER2+ residual invasive disease that is lymph node-negative per the surgical pathology report

6. Evidence of recurrent disease following preoperative therapy and surgery

7. Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons

8. History of exposure to the following cumulative doses of anthracyclines: Doxorubicin > 240 mg/m2; Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) > 480 mg/m2. For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m2.

9. PSN that exceeds grade 1 (mild symptoms)

10. Cardiopulmonary dysfunction

11. Current severe uncontrolled systemic disease

12. Major surgical procedure unrelated to breast cancer or significant traumatic injury within 28 days prior to registration or anticipation of the need for major surgery during the course of study treatment.

13. Screening left ventricular ejection fraction (LVEF) <50% on ECHO or MUGA

Sponsor: 

CRP Contact:  herve.vennin.rendos.ccomtl@ssss.gouv.qc.ca

514-340-8222 ext. 27562

CRP PI: Dr. J. Boileau

Status: Open to accrual