ACE-Breast03: ARX788 in HER2-positive, Metastatic Breast Cancer Subjects (ACE-Breast-03)

Sponsor

Ambrx, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04829604

Collaborator

(none)

210

Enrollment

Locations

Arm

45.9

Anticipated Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Global, Phase 2 Study of ARX788 in HER2-positive, Metastatic Breast Cancer Patients whose Disease is Resistant or Refractory to T-DM1, and/or T-DXd, and/or Tucatinib-containing Regimens

Condition or Disease	Intervention/Treatment	Phase
HER2 Positive Metastatic Breast Cancer	Drug: ARX788	Phase 2

Detailed Description

A Global, Single Arm, Phase 2 Study of ARX788 in HER2-positive, Metastatic Breast Cancer Patients whose disease is Resistant or Refractory to T-DM1, and/or T-DXd, and/or Tucatinib-containing Regimens. The ARX788 will be administered every 3 weeks (Q3W) intravenous (IV) infusion.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

210 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

One single arm, open label with intravenous infusion of ARX788One single arm, open label with intravenous infusion of ARX788

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Global, Phase 2 Study of ARX788 in HER2-positive, Metastatic Breast Cancer Patients Whose Disease is Resistant or Refractory to T-DM-1 or T-DXd, and/or Tucatinib-containing Regimens

Actual Study Start Date :

Apr 5, 2021

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HER2 positive metastatic breast cancer subjects whose disease is resistant or refractory This global Phase 2 study is designed to assess anticancer activity and safety of ARX788 in HER2 positive metastatic breast cancer subjects whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens. The investigational medicinal product (IMP), ARX788, will be administered every 3 weeks (Q3W) by intravenous (IV) infusion.	Drug: ARX788 The active pharmaceutical ingredient in ARX788 is an antibody drug conjugate (ADC) consisting of a humanized anti-HER2 monoclonal antibody (mAb) (IgG1κ) covalently conjugated to two microtubule-disrupting payloads AS269 Other Names: antibody drug conjugate (ADC)

Arm

Intervention/Treatment

Experimental: HER2 positive metastatic breast cancer subjects whose disease is resistant or refractory

This global Phase 2 study is designed to assess anticancer activity and safety of ARX788 in HER2 positive metastatic breast cancer subjects whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens. The investigational medicinal product (IMP), ARX788, will be administered every 3 weeks (Q3W) by intravenous (IV) infusion.

Drug: ARX788

The active pharmaceutical ingredient in ARX788 is an antibody drug conjugate (ADC) consisting of a humanized anti-HER2 monoclonal antibody (mAb) (IgG1κ) covalently conjugated to two microtubule-disrupting payloads AS269

Other Names:

antibody drug conjugate (ADC)

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [2 Years]
The confirmed objective response rate (ORR) of ARX788 based on RECIST 1.1 in HER2-positive breast cancer subjects whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens. The ORR is defined as the number of subjects with a BOR of CR or PR divided by the number of response evaluable subjects.

Secondary Outcome Measures

Duration of response (DOR) [2 years]
DOR is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first, will be computed for subjects with a BOR of CR or PR.
Best percent change in the sum of the longest diameters of measurable tumors [2 years]
The percent change at the best response data point compared to baseline.
Best overall response (BOR) [2 year]
BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started)
Disease control rate (DCR) [2 years]
DCR is defined as the proportion of complete response (CR), partial response (PR), and stable disease (SD) rates.
Progression-free survival (PFS) [2 years]
PFS is defined as the time between date of first dose of study therapy and date of progression or death, whichever occurs first, will be computed for response evaluable subjects. Subjects will be censored at time of subsequent therapy
Overall survival (OS) [2 year]
Overall survival (OS) is defined as the time from first dose of study therapy to the date of death (any cause). Subjects who are alive will be censored at the last known time that the subject was alive.
The number of subjects experiencing adverse event TEAEs [2 years]
Patient safety and adverse events (AEs) will be evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. All AEs and serious adverse events (SAEs) will be assessed to determine the safety and tolerability of the treatment.
Maximum serum concentration (Cmax) for ARX788, total antibody, and pAF-AS269 [Cycle 1 and cycle 3]
Pharmacokinetic parameter maximum serum concentration (Cmax) for ARX788, total antibody, and pAF-AS269
Trough concentration (Ctrough) for ARX788, total antibody, and pAF-AS269 [Cycle 1 and cycle 3]
Pharmacokinetic parameter trough concentration (Ctrough) for ARX788, total antibody, and pAF-AS269
Area under the serum concentration-time curve (AUC) for ARX788, total antibody, and pAF-AS269 [Cycle 1 and cycle 3]
Pharmacokinetic parameter area under the serum concentration-time curve (AUC) for ARX788, total antibody, and pAF-AS269
Incidence of anti-drug antibodies (ADAs) [2 years]
Incidence of anti-drug antibodies (ADAs) following intravenous administration of ARX788 in participants with HER2-positive metastatic breast cancer

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years and older
Life expectancy > 3 months
Eastern Cooperative Oncology Group Performance Status ≤ 1
Metastatic breast cancer subjects previously treated with T DM1, and/or T-DXd, and/or tucatinib-containing regimens.
Presence of at least one measurable lesion per RECIST v 1.1
Subjects must have an adequate tumor sample available for confirmation of HER2 status
Subjects with stable brain metastases
Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade ≤1 as per the NCI-CTCAE v 5.0, except alopecia.
Adequate organ functions
Willing and able to understand and sign an informed consent inform and to comply with all aspects of the protocol.
Female subjects must be surgically sterile, or have a monogamous partner who is surgically sterile, or at postmenopausal, or who commits to use an acceptable form of birth control; male subjects must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control

Exclusion Criteria:

Any subject who meets any of the following criteria is excluded from the study:

History of allergic reactions to any component of ARX788.
Prior history of interstitial lung disease, pneumonitis, or other clinically significant lung disease within 12 months
History of ocular events, or any current ongoing active ocular infections.
History of congestive heart failure, unstable angina pectoris, unstable atrial fibrillation, or cardiac arrhythmia within 12 months prior to enrollment
Grade 3 to 4 peripheral neuropathy (NCI CTCAE v 5.0). Patients with Grade 2 neuropathy can be enrolled at investigator's discretion.
History of unstable central nervous system (CNS) metastases
Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic diseases)
Any uncontrollable intercurrent illness, infection (including subjects with active, symptomatic Covid-19 infections), or other conditions that could limit study compliance or interfere with assessments.
Exposure to any other investigational or commercial anticancer agents or therapies administered with the intention to treat malignancy within 14 days before the first dose of ARX788.
Clinically significant surgical intervention (excluding diagnostic biopsy) within 21 days of the first dose of ARX788
Radiotherapy administered less than 21 days prior to the first dose of ARX788, or localized palliative radiotherapy administered less than 7 days prior to the first dose of ARX788, or radiotherapy-induced toxicity of Grade 2 or greater based on NCI-CTCAE v 5.0.
Pregnancy or breast feeding.
Known active HCV, HBV, and/or HIV infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Glendale	California	United States	92882
2	Research Site	Los Angeles	California	United States	90033
3	Research site	Los Angeles	California	United States	90095
4	Research Site	Santa Barbara	California	United States	93105
5	Research Site	Torrance	California	United States	90505
6	Research Site	West Los Angeles	California	United States	90025
7	Research Site	Newark	Delaware	United States	19713
8	Research Site	Hollywood	Florida	United States	33028
9	Research Site	Orlando	Florida	United States	32806
10	Research Site	Athens	Georgia	United States	30607
11	Research Site	Atlanta	Georgia	United States	30322
12	Research Site	Chicago	Illinois	United States	60611
13	Research Site	Louisville	Kentucky	United States	40207
14	Research Site	Baton Rouge	Louisiana	United States	70809
15	Research Site	Lutherville	Maryland	United States	21093
16	Research Site	Silver Spring	Maryland	United States	20904
17	Research Site	Boston	Massachusetts	United States	02215
18	Research Site	Bolivar	Missouri	United States	65613
19	Research Site	Saint Louis	Missouri	United States	63110
20	Research Site	Omaha	Nebraska	United States	68130
21	Research Site	Las Vegas	Nevada	United States	89128
22	Research Site	Albuquerque	New Mexico	United States	87109
23	Research Site	New York	New York	United States	10016
24	Research Site	New York	New York	United States	10065
25	Research Site	Portland	Oregon	United States	97213
26	Research Site	Tigard	Oregon	United States	97223
27	Research Site	Chattanooga	Tennessee	United States	37404
28	Research Site	Nashville	Tennessee	United States	37203
29	Research Site	Austin	Texas	United States	78731
30	Research Site	Dallas	Texas	United States	75246
31	Research Site	Houston	Texas	United States	77030
32	Research Site	Plano	Texas	United States	75705
33	Research Site	Tyler	Texas	United States	75702
34	Research Site	Norfolk	Virginia	United States	23502
35	Research Site	Tacoma	Washington	United States	98405
36	Research Site	Woolloongabba	Queensland	Australia	4102
37	Research Site	Adelaide	South Australia	Australia	5000
38	Research Site	Clayton	Victoria	Australia	3168
39	Research Site	Frankston	Victoria	Australia	3199
40	University Hospital Geelong	Geelong	Victoria	Australia	3220
41	Research Site	Melbourne	Victoria	Australia
42	Research Site	Ringwood East	Victoria	Australia	3135
43	Research Site	Nedlands	Western Australia	Australia	6009
44	Research Site	Subiaco	Western Australia	Australia	6008
45	Research Site	South Brisbane		Australia	4101
46	Research Site	La Rochelle		France	17019
47	Research Site	Le Mans		France	72000
48	Research Site	Daegu		Korea, Republic of
49	Research Site	Goyang-Si		Korea, Republic of	10408
50	Research Site	Seongnam-si		Korea, Republic of	13496
51	Research Site	Seongnam-si		Korea, Republic of	13620
52	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
53	Research Site	Seoul		Korea, Republic of	03722
54	Research Site	Seoul		Korea, Republic of	05505
55	Research Site	Seoul		Korea, Republic of
56	Research Site	Suwon		Korea, Republic of	16499