What side effects are associated with this type of intervention?

Common side effects of HER2-targeted therapies for breast cancer include decreased neutrophil count, anemia, and nausea. Trastuzumab can cause cardiac issues such as a drop in left ventricular ejection fraction. Trastuzumab emtansine (T-DM1) may lead to fatigue, nausea, and liver function abnormalities. Fam-trastuzumab deruxtecan (T-DXd) is associated with interstitial lung disease, which can be severe and potentially fatal, as well as fatigue, nausea, and diarrhea.

What prior FDA approvals exist?

The FDA has approved several HER2-targeted therapies for the treatment of HER2-positive breast cancer. Trastuzumab (Herceptin) was one of the first, showing significant benefits in progression-free survival (PFS) and overall survival (OS). Pertuzumab, in combination with trastuzumab and docetaxel, has also been approved, demonstrating prolonged PFS and OS without increasing severe adverse events. Ado-trastuzumab emtansine (T-DM1) is another approved option, particularly for patients who have progressed on trastuzumab and chemotherapy. Additionally, lapatinib, a dual tyrosine kinase inhibitor, has been used in combination with other agents, although its benefits are less clear. These therapies highlight the ongoing advancements in targeting HER2 in breast cancer treatment.

What other types of research exist?

Promising novel alternatives to ARX788 for HER2-positive breast cancer patients include: 1) Trastuzumab Deruxtecan (Enhertu), which has shown significant efficacy in previously treated HER2-positive breast cancer. 2) Trastuzumab Emtansine (T-DM1), which combines trastuzumab with a cytotoxic agent and has demonstrated improved outcomes in clinical trials. 3) Pyrotinib, a pan-HER receptor tyrosine kinase inhibitor, which has shown effectiveness in HER2-mutant advanced breast cancer. 4) TAS0728, a covalent-binding, HER2-selective kinase inhibitor, which has shown potent antitumor activity in preclinical models and is under clinical evaluation.

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Monoclonal Antibodies

ARX788 for HER2-Positive Breast Cancer (ACE-Breast03 Trial)

Phase 2

Recruiting

Research Sponsored by Ambrx, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age ≥ 18 years and older

Subjects must have had prior treatment with no more than 5 prior regimens of systemic treatment in the metastatic setting. One of these prior treatments must have been treatment with T-DXd.

Must not have

Any active ocular infections or chronic corneal disorders

Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic diseases)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 year

Awards & highlights

Summary

This trial tests ARX788, a new IV medicine, for patients with HER2-positive metastatic breast cancer who did not respond well to T-DXd. The medicine targets a specific protein on cancer cells to help stop their growth.

Who is the study for?

This trial is for adults with HER2-positive metastatic breast cancer who've had no more than 5 systemic treatments in the metastatic setting, including T-DXd. They must have stable brain metastases, resolved any acute toxicities to Grade ≤1 (except hair loss), and have a measurable lesion. People can't join if they've recently used other cancer treatments, have certain lung or heart conditions, severe uncontrolled diseases, active infections like COVID-19, or unstable brain metastases.

What is being tested?

The study tests ARX788 on patients with advanced breast cancer who previously received T-DXd treatment. It's a global Phase 2 trial focusing on those whose disease has spread and are looking for new treatment options after traditional therapies.

What are the potential side effects?

While specific side effects of ARX788 aren't listed here, common ones may include allergic reactions to its components; it also excludes individuals with histories of significant lung disease suggesting potential respiratory risks.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I've had 5 or fewer treatments for my cancer, including T-DXd.

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I can carry out all my self-care but cannot do heavy physical work.

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My brain cancer has not grown or spread.

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My breast cancer cannot be removed by surgery or has spread.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any ongoing eye infections or long-term corneal problems.

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I do not have any severe illnesses that are not under control.

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I have had lung conditions like interstitial lung disease or pneumonitis.

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I do not have any illnesses that would stop me from following the study plan.

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I have had unstable brain or spinal cord cancer spread.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective response rate (ORR)

Secondary study objectives

Area under the serum concentration-time curve (AUC) for ARX788

Best overall response (BOR)

Disease control rate (DCR)

+6 more

Other study objectives

Evaluate Biomarker

Side effects data

From 2021 Phase 1 & 2 trial • 331 Patients • NCT02257567

65%

FATIGUE

55%

NAUSEA

50%

DIARRHOEA

40%

VOMITING

35%

CONSTIPATION

35%

DYSPNOEA

30%

NEUTROPENIA

30%

DECREASED APPETITE

30%

HEADACHE

25%

UPPER RESPIRATORY TRACT INFECTION

25%

NEUROPATHY PERIPHERAL

20%

THROMBOCYTOPENIA

20%

HYPOMAGNESAEMIA

15%

ALOPECIA

15%

ANAEMIA

15%

DRY MOUTH

15%

BLOOD CREATININE INCREASED

15%

WHITE BLOOD CELL COUNT DECREASED

15%

MUSCULAR WEAKNESS

15%

DIZZINESS

15%

DYSGEUSIA

15%

PERIPHERAL SENSORY NEUROPATHY

15%

PRODUCTIVE COUGH

15%

RASH

15%

DYSPEPSIA

15%

BACK PAIN

15%

HYPOKALAEMIA

10%

CHILLS

10%

OEDEMA PERIPHERAL

10%

UPPER-AIRWAY COUGH SYNDROME

10%

FEBRILE NEUTROPENIA

10%

LYMPHOPENIA

10%

GASTROOESOPHAGEAL REFLUX DISEASE

10%

MUCOSAL INFLAMMATION

10%

PYREXIA

10%

HERPES VIRUS INFECTION

10%

SINUSITIS

10%

URINARY TRACT INFECTION

10%

ALANINE AMINOTRANSFERASE INCREASED

10%

BLOOD ALKALINE PHOSPHATASE INCREASED

10%

BLOOD BILIRUBIN INCREASED

10%

LYMPHOCYTE COUNT DECREASED

10%

WEIGHT DECREASED

10%

HYPERURICAEMIA

10%

HYPOCALCAEMIA

10%

HYPOPHOSPHATAEMIA

10%

ARTHRALGIA

10%

PERIPHERAL MOTOR NEUROPATHY

10%

DEPRESSION

10%

INSOMNIA

10%

DYSURIA

10%

COUGH

10%

DYSPHONIA

10%

NASAL CONGESTION

10%

OROPHARYNGEAL PAIN

10%

FLUSHING

10%

HYPOAESTHESIA

10%

FLATULENCE

10%

ASPARTATE AMINOTRANSFERASE INCREASED

CERVICAL SPINAL STENOSIS

HAEMOLYSIS

SINUS TACHYCARDIA

EYE PRURITUS

VISION BLURRED

ABDOMINAL DISCOMFORT

ANAL SPASM

DEFAECATION URGENCY

INFECTION

GINGIVAL DISORDER

OESOPHAGEAL CANDIDIASIS

PARONYCHIA

GINGIVAL PAIN

HAEMATOCHEZIA

HAEMORRHOIDS

LIP DRY

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

ACUTE KIDNEY INJURY

ACUTE PULMONARY OEDEMA

HYPOXIA

ABDOMINAL DISTENSION

STOMATITIS

PAIN

HERPES ZOSTER

LIPASE INCREASED

HYPERSENSITIVITY

PLATELET COUNT DECREASED

DEHYDRATION

HYPERGLYCAEMIA

PAIN IN EXTREMITY

PARAESTHESIA

POST HERPETIC NEURALGIA

ANXIETY

POLLAKIURIA

DYSPNOEA EXERTIONAL

PRURITUS

RASH MACULO-PAPULAR

HYPERTENSION

ESCHERICHIA URINARY TRACT INFECTION

LOWER RESPIRATORY TRACT INFECTION

ORAL CANDIDIASIS

COMMINUTED FRACTURE

WOUND

TROPONIN I INCREASED

HYPOGLYCAEMIA

HYPONATRAEMIA

INTERVERTEBRAL DISC DEGENERATION

MUSCULOSKELETAL STIFFNESS

TUMOUR PAIN

LETHARGY

NEURALGIA

SINUS HEADACHE

MENTAL STATUS CHANGES

URINARY RETENTION

VAGINAL DISCHARGE

PULMONARY OEDEMA

SINUS PAIN

DERMATITIS

EMBOLISM

ENDOMETRIAL ADENOCARCINOMA

LEUKOPENIA

SEIZURE

RHINORRHOEA

HAEMOLYTIC ANAEMIA

IRRITABILITY

HYPOGAMMAGLOBULINAEMIA

LYMPHADENOPATHY

PNEUMONIA

INFUSION RELATED REACTION

HYPOALBUMINAEMIA

RASH MACULAR

100%

80%

60%

40%

20%

Study treatment Arm

Arm E (Phase II Expansion): Pola+BG in FL

Cohort 1a (Phase Ib Safety Run-In): Pola+BR in DLBCL

Cohort 1a (Phase Ib Safety Run-In): Pola+BR in FL

Cohort 1b (Phase Ib Safety Run-In): Pola+BG in FL

Cohort 1b (Phase Ib Safety Run-In): Pola+BG in DLBCL

Arm A (Phase II Randomization): Pola+BR in FL

Arm B (Phase II Randomization): BR in FL

Arm C (Phase II Randomization): Pola+BR in DLBCL

Arm D (Phase II Randomization): BR in DLBCL

Arm F (Phase II Expansion): Pola+BG in DLBCL

Arm G+H (Phase II NF Cohort): Pola+BR in DLBCL

Trial Design

1Treatment groups

Experimental Treatment

Group I: ARX788Experimental Treatment1 Intervention

The investigational medicinal product (IMP), ARX788, will be administered every 3 weeks (Q3W) by intravenous (IV) infusion.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ARX788

2018

Completed Phase 1

~110

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

HER2-targeted therapies, such as trastuzumab, pertuzumab, and ARX788, work by specifically targeting the HER2 protein, which is overexpressed in some breast cancer cells. Trastuzumab binds to the HER2 receptor, inhibiting cell proliferation and promoting immune-mediated destruction of the cancer cells. Pertuzumab also targets HER2 but binds to a different site, preventing receptor dimerization and subsequent signaling. ARX788 is an antibody-drug conjugate that delivers cytotoxic agents directly to HER2-positive cells, enhancing cell death. These therapies are crucial for patients with HER2-positive breast cancer as they improve survival rates and reduce disease progression by specifically targeting cancer cells while sparing normal cells.