HER2CLIMB-05: A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer

Sponsor

Seagen Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05132582

Collaborator

Merck Sharp & Dohme LLC (Industry)

650

Enrollment

Locations

Arms

63.8

Anticipated Duration (Months)

17.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is being done to see if tucatinib works better than placebo when given with other drugs to treat participants with HER2-positive breast cancer. A placebo is a pill that looks the same as tucatinib but has no medicine in it. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.

Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic).

In this study, all participants will get either tucatinib or placebo. Participants will be assigned randomly to a group. This is a blinded study, so patients and their doctors will not know which group a participant is in.

All participants will also get trastuzumab and pertuzumab. These are 2 drugs used to treat this type of cancer.

Condition or Disease	Intervention/Treatment	Phase
HER2 Positive Breast Cancer	Drug: Tucatinib Drug: Trastuzumab Drug: Pertuzumab Drug: Combination product: Trastuzumab + Pertuzumab Drug: Placebo	Phase 3

Detailed Description

Control arm: Placebo given orally twice daily plus trastuzumab and pertuzumab every 21 days

Experimental arm: Tucatinib 300 mg given orally twice daily plus trastuzumab and pertuzumab every 21 days

Trastuzumab and pertuzumab will be administered as follows:

• Trastuzumab will be given intravenously (IV) at a dose of 6 mg/kg or subcutaneously (SC) at a fixed dose of 600 mg, once every 21 days.

AND

Pertuzumab will be given IV at 420 mg every 21 days. OR
Fixed dose combination of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given SC, once every 21 days, in lieu of trastuzumab and pertuzumab individually.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

650 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for Metastatic HER2+ Breast Cancer (HER2CLIMB-05)

Actual Study Start Date :

Mar 7, 2022

Anticipated Primary Completion Date :

Oct 31, 2024

Anticipated Study Completion Date :

Jun 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tucatinib + trastuzumab + pertuzumab Tucatinib + trastuzumab + pertuzumab	Drug: Tucatinib 300mg given by mouth (orally) twice daily Other Names: TUKYSA, ONT-380, ARRY-380 Drug: Trastuzumab 6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days Other Names: Herceptin, Herceptin Hylecta Drug: Pertuzumab 420mg given by IV every 21 days Other Names: Perjeta Drug: Combination product: Trastuzumab + Pertuzumab 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days. May be given in place of trastuzumab and pertuzumab individually. Other Names: Phesgo
Active Comparator: Placebo + trastuzumab + pertuzumab Placebo + trastuzumab + pertuzumab	Drug: Trastuzumab 6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days Other Names: Herceptin, Herceptin Hylecta Drug: Pertuzumab 420mg given by IV every 21 days Other Names: Perjeta Drug: Combination product: Trastuzumab + Pertuzumab 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days. May be given in place of trastuzumab and pertuzumab individually. Other Names: Phesgo Drug: Placebo Given orally twice daily

Arm

Intervention/Treatment

Experimental: Tucatinib + trastuzumab + pertuzumab

Tucatinib + trastuzumab + pertuzumab

Drug: Tucatinib

300mg given by mouth (orally) twice daily

Other Names:

TUKYSA, ONT-380, ARRY-380

Drug: Trastuzumab

6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days

Other Names:

Herceptin, Herceptin Hylecta

Drug: Pertuzumab

420mg given by IV every 21 days

Other Names:

Perjeta

Drug: Combination product: Trastuzumab + Pertuzumab

600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days. May be given in place of trastuzumab and pertuzumab individually.

Other Names:

Phesgo

Active Comparator: Placebo + trastuzumab + pertuzumab

Placebo + trastuzumab + pertuzumab

Drug: Trastuzumab

6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days

Other Names:

Herceptin, Herceptin Hylecta

Drug: Pertuzumab

420mg given by IV every 21 days

Other Names:

Perjeta

Drug: Combination product: Trastuzumab + Pertuzumab

600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days. May be given in place of trastuzumab and pertuzumab individually.

Other Names:

Phesgo

Drug: Placebo

Given orally twice daily

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Up to approximately 3 years]
The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause

Secondary Outcome Measures

Overall survival (OS) [Up to approximately 5 years]
The time from randomization to death from any cause.
PFS by blinded independent central review (BICR) per RECIST v1.1 [Up to approximately 3 years]
The time from the date of randomization to the documented disease progression assessed by BICR according to RECIST v1.1 or death from any cause
Time to deterioration of health-related quality of life (HRQoL) [Up to approximately 3 years]
Will be measured based on patient reported outcomes (PROs) according to the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ C30).
Central nervous system (CNS) PFS [Up to approximately 3 years]
The time from randomization to investigator assessed disease progression in brain (RECIST v1.1), or death from any cause
Incidence of adverse events (AEs) [Through 30 days after last study treatment, approximately 18 months]
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Incidence of laboratory abnormalities [Through 30 days after last study treatment, approximately 18 months]
To be summarized using descriptive statistics.
Incidence of tucatinib dose alterations [Through 30 days after last study treatment, approximately 18 months]
To be summarized using descriptive statistics.
Incidence of trastuzumab dose alterations [Through 30 days after last study treatment, approximately 18 months]
To be summarized using descriptive statistics.
Incidence of pertuzumab dose alterations [Through 30 days after last study treatment, approximately 18 months]
To be summarized using descriptive statistics.
Maximum concentration (Cmax) [Through 30 days after last study treatment, approximately 18 months]
To be summarized using descriptive statistics.
Trough concentration (Ctrough) [Through 30 days after last study treatment, approximately 18 months]
To be summarized using descriptive statistics.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Centrally confirmed HER2+ breast carcinoma per 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines.
Have unresectable locally advanced or metastatic disease.
If recurrent (after [neo]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab or pertuzumab received for advanced HER2+ disease.
Have received 4-8 cycles (21 day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression
Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-])
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants may have any of the following:
No evidence of brain metastases
Untreated brain metastases which are asymptomatic and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane
Previously treated brain metastases which are asymptomatic
Brain metastases previously treated with local therapy must not have progressed since treatment

Exclusion Criteria:

Prior treatment with any anti-HER2 and/or anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and ≥ 12 months have elapsed since last neratinib dose prior to start of study drug)
Unable to undergo contrast MRI of the brain
CNS Exclusion - Based on screening brain MRI and clinical assessment
Symptomatic brain metastasis
Progression of brain metastases since starting first line trastuzumab, pertuzumab, and taxane
Ongoing use of systemic corticosteroids at a total daily dose of >2 mg of dexamethasone (or equivalent)
Any untreated brain lesion in an anatomic site which may pose risk to participant
Known or suspected leptomeningeal disease (LMD)
Poorly controlled (>1/week) seizures, or other persistent neurologic symptoms

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Medical Center / David Geffen School of Medicine	Santa Monica	California	United States	90404
2	Mayo Clinic Florida	Jacksonville	Florida	United States	32224
3	AdventHealth Cancer Institute	Orlando	Florida	United States	32804
4	Orlando Health, Inc. TRIO	Orlando	Florida	United States	32806
5	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii	United States	96819
6	University of Illinois at Chicago	Chicago	Illinois	United States	60612
7	Norton Cancer Institute	Louisville	Kentucky	United States	40202
8	Norton Cancer Institute	Louisville	Kentucky	United States	40207
9	Norton Cancer Institute	Louisville	Kentucky	United States	40241
10	Mercy Medical Center -Weinberg Center	Baltimore	Maryland	United States	21202
11	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
12	Saint Luke's Cancer Institute LLC	Kansas City	Missouri	United States	64113
13	Nebraska Cancer Specialists	Grand Island	Nebraska	United States	68803
14	Oncology Hematology West, P.C.	Omaha	Nebraska	United States	68130
15	Monmouth Medical Center Southern Campus	Lakewood	New Jersey	United States	08701
16	Saint Barnabas Medical Center Cancer Center	Livingston	New Jersey	United States	07039
17	Monmouth Medical Center	Long Branch	New Jersey	United States	07740
18	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903-2681
19	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey	United States	08876
20	Community Medical Center	Toms River	New Jersey	United States	08755
21	Montefiore Medical Center	Bronx	New York	United States	10461
22	Cleveland Clinic Lerner College of Medicine	Cleveland	Ohio	United States	44195
23	Zangmeister Cancer Center	Columbus	Ohio	United States	43219
24	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
25	Thomas Jefferson University	Willow Grove	Pennsylvania	United States	19090
26	Charleston Oncology	Charleston	South Carolina	United States	29414
27	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
28	Seattle Cancer Care Alliance / University of Washington	Seattle	Washington	United States	98109
29	Medical College of Wisconsin (Milwaukee)	Milwaukee	Wisconsin	United States	53226
30	Austin Health	Heidelberg	Other	Australia	3084
31	University of Alberta / Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
32	Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
33	Sunnybrook Odette Cancer Centre	Toronto	Ontario	Canada	M4N3M5
34	Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz	Besancon Cedex	Other	France	25000
35	National Hospital Organization Hokkaido Cancer Center	Sapporo-shi	Other	Japan	003-0804
36	Przychodnia Lekarska KOKMED Roman Karaszewski	Konin	Other	Poland	62-500
37	Hospital General Universitario Alicante	Alicante	Other	Spain	03010