What side effects are associated with this type of intervention?

Common treatments for breast cancer, such as chemotherapy, endocrine therapy, and targeted therapies, have a range of side effects. Chemotherapy can cause alopecia, neurotoxicity, granulocytopenia, anemia, and gastrointestinal issues. Endocrine therapies like tamoxifen and aromatase inhibitors can lead to hot flashes, bone density loss, cardiovascular risks, and other menopausal symptoms. Targeted therapies may cause specific toxicities depending on the agent, such as skin rashes, diarrhea, and liver function abnormalities. These side effects vary in severity and frequency, and patient tolerance should be regularly assessed.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer, including single agents and combination therapies. Hormonal therapies such as tamoxifen and aromatase inhibitors (e.g., letrozole, anastrozole) are commonly used for hormone receptor-positive breast cancer. Targeted therapies include HER2 inhibitors like trastuzumab and pertuzumab, as well as CDK4/6 inhibitors like palbociclib. Immunotherapies, such as pembrolizumab, have also been approved for certain types of breast cancer. These treatments work through various mechanisms, including hormone receptor modulation, inhibition of specific growth factor receptors, and immune checkpoint blockade.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include: <ol> <li>PI3K/PTEN/AKT/mTOR pathway inhibitors such as temsirolimus and everolimus, which have shown potential in clinical trials.</li> <li></li> </ol> Selective RET inhibitors like selpercatinib and pralsetinib, particularly for patients with RET-altered tumors. 3. Antiangiogenic kinase inhibitors targeting mutated RET kinase, which have demonstrated utility in advanced metastatic cases. 4. PARP inhibitors like olaparib and talazoparib for patients with germline BRCA mutations. 5. Novel combinations involving docetaxel and trastuzumab, which are being explored for their synergistic effects.

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Monoclonal Antibodies

New Treatments for Metastatic Breast Cancer (PRE-I-SPY-PI Trial)

Phase 1

Recruiting

Led By Paula R Pohlmann, MD, MSc, PhD

Research Sponsored by QuantumLeap Healthcare Collaborative

Eligibility Criteria Checklist

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

Must have

ECOG performance status Grade 0-2

Age ≥ 18 years at the time of signing the informed consent

Must not have

Liver disease: Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis

Uncontrolled intercurrent illness including active infection, diabetes, pulmonary embolism in the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements

Timeline

Screening 3 weeks

Treatment Varies

Follow Up start of treatment to 12 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing different medicines or combinations of medicines to treat cancer. It focuses on patients with certain solid tumors, including breast cancer. The study aims to find the safest and most effective dose and then tests that dose on more patients to see if it works. Dinaciclib is being evaluated for its potential in combination therapies for breast cancer.

Who is the study for?

This trial is for adults with breast cancer who have a life expectancy over 12 weeks and can follow the study plan. They must not be pregnant, should agree to use contraception, and have recovered from previous treatments. People with uncontrolled brain cancer, recent major surgery, or severe illnesses that affect study participation cannot join.

What is being tested?

The I-SPY Phase I/Ib trial tests new drugs (Tucatinib, Zanidatamab, Fam-Trastuzumab Deruxtecan-Nxki, ALX148) alone or in combinations for metastatic breast cancer. It aims to identify effective treatments quickly for further trials.

What are the potential side effects?

Potential side effects are not specified but may include typical reactions to cancer medications such as nausea, fatigue, blood count changes, allergic reactions and possibly organ-specific issues depending on each drug's profile.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself and perform daily activities.

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I am 18 years old or older.

Exclusion Criteria

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

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I have a significant history of liver disease, including hepatitis, alcohol abuse, or cirrhosis.

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I do not have any uncontrolled illnesses or social situations that would affect my study participation.

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I do not have active or uncontrolled brain or spinal cord cancer.

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I have not had major surgery in the last 4 weeks.

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I have had significant heart problems in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ start of treatment to 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~start of treatment to 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and start of treatment to 12 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Duration of Response (DOR)

Incidence of Adverse Events related to the treatment

Incidence of Dose Limiting Toxicities (DLTs) at each dose level

+3 more

Secondary study objectives

Clinical Benefit Rate (CBR) at 6 months

Progression Free Survival (PFS) - descriptive

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: PRE2 Zanidatamab (ZW25, zani) + Tucatinib (TUKYSA®)Experimental Treatment2 Interventions

Zanidatamab is a bispecific IgG1-like antibody directed against two distinct HER2 epitopes. It induces formation of receptor clusters and internalization resulting in downregulation. It also inhibits growth factor-dependent and -independent tumor cell proliferation as well as potently activating ADCC, ADCP, and CDC. Tucatinib is a highly selective, small molecule tyrosine kinase inhibitor (TKI) of HER2 compared to other TKI's (i.e., EGFR). It is well tolerated, crosses the blood brain barrier and can treat CNS disease. It is FDA approved for HER2+ breast cancer. Given the promising clinical data for each of these drugs which have different mechanisms, the effect of zanidatamab after T-DXd (Enhertu®) in breast cancer patients, and the favorable toxicity profile of both drugs, we hypothesize that the combination of tucatinib and zanidatamab will be well tolerated and more efficacious than either drug alone for the treatment of patients with HER2 positive breast cancer.

Group II: PRE1 ALX148 (Evorpacept) + Fam-Trastuzumab Deruxtecan-Nxki (T-DXd, Enhertu®)Experimental Treatment2 Interventions

The combination of T-DXd and ALX148 aims to explore the anti-tumoral effects of trastuzumab, of the topoisomerase inhibitor DXd and of the CD47-blocking agent ALX148. The rationale for this combination is that ALX148 is hypothesized, based on preclinical data, to facilitate antibody-dependent cellular phagocytosis (ADCP) of HER2 expressing (\>HER2 1+) breast cancer binding T-DXd while cancer cell intrinsic or bystander cytotoxicity of T-DXd will result in the release of neoantigens promoting immune mediated antitumor activity in the tumor microenvironment.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Zanidatamab

2020

Completed Phase 2

~80

Tucatinib

2017

Completed Phase 2

~800

0 / 7Eligibility 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

Breast cancer treatments include endocrine therapy, chemotherapy, and targeted therapy. Endocrine therapy, like aromatase inhibitors, reduces estrogen levels to slow the growth of hormone receptor-positive cancers. Chemotherapy uses cytotoxic agents to kill rapidly dividing cells, including cancer cells. Targeted therapies, such as CDK4/6 inhibitors, block specific proteins involved in cell cycle regulation to prevent cancer cell proliferation. Understanding these mechanisms helps tailor treatments to the tumor's characteristics, improving efficacy and minimizing unnecessary side effects.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Inference of synergy/antagonism between anticancer drugs from the pooled analysis of clinical trials.Phase I design for completely or partially ordered treatment schedules.