AB-201 for Advanced HER2+ Breast Cancer

Recruiting at 1 trial location

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

133 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial will enroll subjects with HER2+ solid tumors and is conducted in two phases. The primary objective of Phase 1 is to determine the safety and tolerability of AB-201 in subjects with advanced HER2+ solid tumors. The primary objective of Phase 2 is to evaluate the efficacy of AB-201. Subjects will receive up to 3 doses of AB-201, followed by scheduled assessments of overall health and tumor response.

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.

What data supports the effectiveness of the drug AB-201 for advanced HER2+ breast cancer?

The research highlights the effectiveness of several anti-HER2 drugs, such as trastuzumab deruxtecan and tucatinib, which have shown significant improvements in survival for patients with advanced HER2+ breast cancer. These advancements suggest that new drugs targeting HER2, like AB-201, could potentially offer similar benefits. ^{1 2 3 4 5}

What safety data exists for AB-201 or similar treatments for advanced HER2+ breast cancer?

HER2-targeted therapies for breast cancer can improve survival but may cause side effects like blood, heart, lung, and digestive issues. Molecular target anticancer drugs, which include treatments like AB-201, have been shown to increase the risk of serious and fatal side effects compared to placebo. ^{6 7 8 9 10}

What makes the drug AB-201 unique for treating advanced HER2+ breast cancer?

AB-201 is a novel treatment for advanced HER2+ breast cancer, potentially offering a new approach compared to existing therapies like trastuzumab and lapatinib, which face resistance issues. While specific details about AB-201 are not provided, it may involve innovative strategies such as higher drug-to-antibody ratios or new mechanisms of action, similar to recent advancements in HER2-targeting treatments. ^{1 2 4 11 12}

Research Team

Thorsten Graef, MD, Ph.D

Principal Investigator

Artiva Biotherapeutics

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Targeting HER2 in breast cancer: new drugs and paradigms on the horizon. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The trastuzumab era: current and upcoming targeted HER2+ breast cancer therapies. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Third-line treatment of HER2-positive advanced breast cancer: From no standard to a Pandora's box. [2021]

4. Spain pubmed.ncbi.nlm.nih.gov

Lapatinib ditosylate: expanding therapeutic options for receptor tyrosine-protein kinase erbB-2-positive breast cancer. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. [2023]

6. India 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. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Overcoming treatment challenges in advanced breast cancer. [2018]

8. England 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. [2023]

9. Netherlands 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. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Incidence of adverse events with therapies targeting HER2-positive metastatic breast cancer: a literature review. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

The emerging role of lapatinib in HER2-positive breast cancer. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Beyond trastuzumab and lapatinib: new options for HER2-positive breast cancer . [2022]