AB-201 for Advanced HER2+ Breast Cancer

No longer recruiting at 2 trial locations

Overseen By AB-201-01 Study Team

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Artiva Biotherapeutics, Inc.

Must not be taking: Antibiotics, Antifungals, Antivirals

Disqualifiers: Other malignancy, Cardiac disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AB-201, a potential drug for individuals with advanced HER2+ breast and gastric cancer. Phase 1 focuses on assessing the safety and tolerability of AB-201. Phase 2 will evaluate the treatment's effectiveness in addressing these cancers. This trial may suit those with HER2+ breast or gastric cancer that hasn't responded to other treatments or has limited options. Participants will receive up to three doses of AB-201 and undergo regular health and tumor assessments. As a Phase 1 trial, participants will be among the first to receive this treatment, contributing to understanding its safety and tolerability.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that AB-201 is likely to be safe for humans?

Research shows that AB-201 is undergoing safety testing in patients with advanced HER2+ breast cancer. Previous studies on similar treatments targeting HER2 (a protein found in some cancer cells) have shown that these treatments can be well-tolerated. However, some patients experienced side effects like tiredness, nausea, and lower blood cell counts.

Researchers are still testing AB-201 to better understand its safety. The trial is in the early stages, focusing on ensuring the treatment is safe and well-tolerated by patients. This step is crucial before determining the treatment's effectiveness.

In summary, while some safety information exists from similar treatments, AB-201 is still under close study to confirm its safety in humans. Researchers will monitor participants to manage any side effects effectively. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AB-201 because it targets HER2+ advanced breast cancer in ways that current treatments may not. Unlike standard therapies like trastuzumab or pertuzumab, AB-201 may offer an alternative for patients who are resistant or intolerant to these treatments. AB-201 is designed to work even when previous treatments have failed, targeting specific HER2 overexpressions (IHC ≥2+ and IHC 3+ or IHC 2+/ISH+). This precision in targeting makes it a promising option for individuals who have limited options left, potentially improving outcomes where other treatments fall short.

What evidence suggests that AB-201 might be an effective treatment for advanced HER2+ breast cancer?

Research shows that targeting HER2, a protein found in high levels in some cancers, has successfully treated HER2-positive breast cancer. Studies have demonstrated that focusing on HER2 can greatly improve survival rates. For instance, using two treatments that target HER2 resulted in a median survival of over 57 months in advanced cases. In this trial, AB-201 is being tested as a newer treatment targeting this pathway, offering hope for those who haven't responded well to other treatments. Early research on similar treatments is promising, suggesting that AB-201 could effectively manage HER2-positive cancers, even those resistant to standard therapies. ^{1 3 5 6 7}

Who Is on the Research Team?

Thorsten Graef, MD, Ph.D

Principal Investigator

Artiva Biotherapeutics

Are You a Good Fit for This Trial?

This trial is for adults with advanced HER2+ breast or gastric/GEJ cancer who've had prior treatments but their disease didn't respond or they couldn't tolerate the treatment. They should be relatively healthy (ECOG 0-1) and not have other cancers, serious heart issues, active brain metastases, or severe health decline recently.

Inclusion Criteria

Must have received prior cancer therapy: Subjects with breast cancer must have received ≥ 2 prior systemic therapies; subjects with gastric/GEJ cancer must have received ≥ 1 prior systemic therapy(ies); subjects with IHC 3+ or IHC 2+/ISH+ cancers must have received previous treatment with a HER2-targeting therapy

I am fully active or can carry out light work.

My cancer is HER2 positive, confirmed by a test within the last 6 months.

Exclusion Criteria

I have or had cancer types other than the one I'm seeking treatment for.

I have a known heart condition.

I still have side effects from previous cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Determine the safety and tolerability of AB-201 in subjects with advanced HER2+ solid tumors

Up to 3 doses

Phase 2 Treatment

Evaluate the efficacy of AB-201 in subjects with advanced HER2+ solid tumors

Up to 3 doses

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AB-201

Trial Overview The trial tests AB-201's safety and tumor-fighting ability in two phases. Phase 1 checks how safe it is for people with advanced HER2+ tumors; Phase 2 looks at how well it works. Participants will get up to three doses of AB-201 along with assessments of their health and tumor response.

How Is the Trial Designed?

Group I: Phase 2 Cohort C Experimental Treatment 3 Interventions

AB-201 given to patients with advanced/unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression (IHC ≥ 2+) that is refractory to or intolerant of standard treatment, or for which no standard treatment is available

Group II: Phase 2 Cohort B Experimental Treatment 3 Interventions

AB-201 given to patients with advanced/unresectable or metastatic breast cancer with HER2 overexpression (IHC 3+ or IHC 2+/ISH+) that is relapsed to, refractory to, or intolerant of previous trastuzumab deruxtecan (T-DXd) based therapy

Group III: Phase 2 Cohort A Experimental Treatment 3 Interventions

AB-201 given to patients with advanced/unresectable or metastatic breast cancer with HER2 overexpression (IHC ≥2+) that is refractory to or intolerant of standard treatment, or for which no standard treatment is available

Group IV: Phase 1 Dose Confirmation Experimental Treatment 3 Interventions

Dose Confirmation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression

Who Is Running the Clinical Trial?

Artiva Biotherapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

520+

Published Research Related to This Trial

In a phase II study involving 87 female patients with metastatic breast cancer who had previously failed HER2-targeted therapy, afatinib alone resulted in an objective response rate of 18%.

When afatinib was combined with vinorelbine or paclitaxel for patients who progressed on afatinib monotherapy, the objective response rate increased to 31%, with manageable side effects and no significant additional toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afatinib alone and in combination with vinorelbine or paclitaxel, in patients with HER2-positive breast cancer who failed or progressed on prior trastuzumab and/or lapatinib (LUX-Breast 2): an open-label, multicenter, phase II trial. Hickish, T., Mehta, A., Liu, MC., et al.[2022]

HER2-positive metastatic breast cancer is more aggressive and often develops resistance to treatments compared to HER2-negative tumors, making effective management crucial.

Trastuzumab is the standard treatment for HER2-positive cases, but lapatinib has been developed as a targeted therapy that works inside the cell to disrupt harmful signaling pathways, offering a potential solution to overcome resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming treatment challenges in advanced breast cancer. Harkins, B., Geyer, CE.[2018]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

HER2-positive breast cancer, which historically had a poor prognosis, can now be effectively treated with a variety of anti-HER2 therapies, significantly improving patient survival rates.

Newly developed treatments, including trastuzumab deruxtecan and trastuzumab emtansine, along with ongoing clinical trials, are expanding options for patients with advanced HER2-positive breast cancer, raising important questions about the best treatment sequences and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. Stanowicka-Grada, M., Senkus, E.[2023]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12327481/

Management of advanced-stage HER2+ breast cancer Human Epidermal Growth Factor Receptor 2 (HER2) overexpression or amplification is found in 15–20% of invasive breast cancers.

2. academic.oup.com academic.oup.com/oncolo/article/30/4/oyae280/8107614

Treatment patterns and associated outcomes among patients ... In this real-world study of 2074 patients treated for HER2+ mBC, 87.4% received anti-HER2-based therapy in 1L; however, this is higher than in a ...

3. nature.com nature.com/articles/s41573-022-00579-0

Targeting HER2-positive breast cancer: advances and ... Currently, survival rates exceed 90% in HER2+ early breast cancer (EBC) treated with chemotherapy and dual antibody therapy5. More than half of ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1040842825000125

Challenges and prospects in HER2-positive breast cancer ... In metastatic breast cancer, although the CLEOPATRA trial reported an unprecedented median survival of 57.1 months with dual HER2-targeted therapy combined with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10020272/

Outcomes for the first four lines of therapy in patients with ... In HR-/HER2 + disease, 91–96% of patients received chemotherapy and 77–91% HER2-targeted therapy, irrespective of line of therapy. In patients ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06914661

Efficacy and Safety of DS8201 in Metastatic Breast ... The aim of this study is to analyze the real-world clinical trial data to investigate the efficacy and safety of DS8201-containing formula in the treatment of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10927773/

Molecular probes targeting HER2 PET/CT and their ... Anti-HER2-targeted treatment has been repeatedly linked to improvements in disease-free and overall survival in advanced breast cancer patients ...