Your session is about to expire
← Back to Search
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 belowSelect...
I can take care of myself and perform daily activities.
Select...
I am 18 years old or older.
Exclusion Criteria
You may be eligible for the trial if you check “No” for criteria below:Select...
I have a significant history of liver disease, including hepatitis, alcohol abuse, or cirrhosis.
Select...
I do not have any uncontrolled illnesses or social situations that would affect my study participation.
Select...
I do not have active or uncontrolled brain or spinal cord cancer.
Select...
I have not had major surgery in the last 4 weeks.
Select...
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
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 moreSecondary 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
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.
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.
Find a Location
Who is running the clinical trial?
QuantumLeap Healthcare CollaborativeLead Sponsor
5 Previous Clinical Trials
6,923 Total Patients Enrolled
1 Trials studying Breast Cancer
5,000 Patients Enrolled for Breast Cancer
Paula R Pohlmann, MD, MSc, PhDPrincipal InvestigatorM.D. Anderson Cancer Center
2 Previous Clinical Trials
19 Total Patients Enrolled
Media Library
Eligibility Criteria:
This trial includes the following eligibility criteria:- I have a significant history of liver disease, including hepatitis, alcohol abuse, or cirrhosis.You are in a place because of a legal order, such as prison or a mental health facility.I do not have any uncontrolled illnesses or social situations that would affect my study participation.You have had a bad reaction to a medication before.I can take care of myself and perform daily activities.I do not have active or uncontrolled brain or spinal cord cancer.I am 18 years old or older.My recent tests show my organs are working well.I haven't had any cancer treatments recently.I have not had major surgery in the last 4 weeks.I have recovered from previous cancer treatments with minimal side effects.I am willing to use birth control during the study.I am a man or a woman, whether before or after menopause.I have had significant heart problems in the last 6 months.
Research Study Groups:
This trial has the following groups:- Group 1: PRE1 ALX148 (Evorpacept) + Fam-Trastuzumab Deruxtecan-Nxki (T-DXd, Enhertu®)
- Group 2: PRE2 Zanidatamab (ZW25, zani) + Tucatinib (TUKYSA®)
Awards:
This trial has 1 awards, including:- No Placebo-Only Group - All patients enrolled in this study will receive some form of active treatment.
Timeline:
This trial has the following timeline:- Screening: It may take up to 3 Weeks to process to see if you qualify in this trial.
- Treatment: The duration you will receive the treatment varies.
- Follow Ups: You may be asked to continue sharing information regarding the trial for 6 Months after you stop receiving the treatment.
Share this study with friends
Copy Link
Messenger