Pidnarulex + Trastuzumab Deruxtecan for HER2-Positive Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Interstitial lung disease, Severe pulmonary compromise, Recent chemotherapy, others

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

Compensation: Varies

Number of Visits: 72

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with certain types of breast cancer and other solid tumors that have spread or cannot be surgically removed. The trial combines two drugs: pidnarulex, which inhibits cancer cell growth, and trastuzumab deruxtecan, which targets and kills cancer cells with the HER2 protein. The goal is to determine the safest and most effective dose of these drugs when used together. This trial may suit someone whose breast cancer has spread or is advanced, especially if standard treatments are no longer viable. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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

The trial does not specify if you need to stop taking your current medications, but it does exclude participants taking strong CYP3A4 inhibitors or inducers, as these can affect the trial drugs. It's best to discuss your current medications with the trial team to see if they might interact with the study drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pidnarulex has potential benefits in early studies, aiding patients with specific genetic mutations linked to breast and ovarian cancer. However, it remains in the early stages of testing to determine its safety and tolerability.

In contrast, trastuzumab deruxtecan is already in medical use. Studies confirm its general safety, though side effects can occur. Approximately 7% of patients discontinued its use due to these effects, and around 13% experienced lung problems known as interstitial lung disease (ILD).

Overall, while pidnarulex is still under close study, trastuzumab deruxtecan has more established safety data, though some side effects are significant. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Pidnarulex + Trastuzumab Deruxtecan for HER2-positive breast cancer because it introduces a new approach to tackling this aggressive form of cancer. While most treatments focus on blocking the HER2 receptor, Pidnarulex works by targeting and disrupting the DNA repair process in cancer cells, potentially leading to more effective cancer cell death. Trastuzumab Deruxtecan, on the other hand, is an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, minimizing damage to healthy cells. This combination could enhance treatment effectiveness while reducing side effects compared to traditional chemotherapy.

What evidence suggests that this treatment might be an effective treatment for HER2-positive breast cancer?

Research has shown that trastuzumab deruxtecan yields promising results for treating HER2-positive breast cancer. In one study, 67.3% of patients experienced complete tumor disappearance. Another study found that 35.9% of patients saw tumor shrinkage. In this trial, participants will receive a combination of trastuzumab deruxtecan and pidnarulex.

Pidnarulex blocks an enzyme, causing cancer cells to die and stopping tumor growth. This trial tests whether pidnarulex can enhance the effectiveness of treatments like trastuzumab deruxtecan. Although human data on pidnarulex is limited, its mechanism suggests potential benefits when combined with other treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

Filipa Lynce

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic HER2-positive breast cancer or other solid tumors that can't be removed by surgery. Participants must have a certain level of physical fitness (ECOG ≤ 2), adequate blood cell counts, and normal liver function. Children and those who've recently received blood transfusions or growth factors are excluded.

Inclusion Criteria

I have confirmed breast cancer that is advanced or has spread.

Absolute neutrophil count (ANC) ≥ 1,500/mcL

International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN

Exclusion Criteria

Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous

I am allergic to certain drugs similar to CX-5461, T-DXd, or their ingredients.

Patients with a corrected QT interval (QTc) prolongation to > 470 ms (females) or > 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of pidnarulex in combination with trastuzumab deruxtecan

Up to completion of dose-escalation

Visits every 21 days per cycle

Dose Expansion

Evaluate safety and tolerability of the combination at the RP2D in patients with HER2-low breast cancer

21-day cycles

Visits every 21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Follow-up at 30 days post-treatment, then regular visits

What Are the Treatments Tested in This Trial?

Interventions

• Pidnarulex
• Trastuzumab Deruxtecan

Trial Overview

The trial is testing the combination of two anti-cancer drugs: Pidnarulex, which inhibits enzymes to stop tumor growth, and Trastuzumab Deruxtecan, an antibody-drug conjugate targeting HER2 positive cells to deliver chemotherapy directly. The study aims to determine safety, side effects, and optimal dosing.

How Is the Trial Designed?

Group I: Treatment (Pidnarulex, T-DXd) Experimental Treatment 7 Interventions

Patients receive pidnarulex IV over 60 minutes on day 8 of each cycle and T-DXd IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, collection of blood samples, and radiologic imaging throughout the trial. Patients may also undergo biopsy throughout the trial.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1.

clinicaltrialsarena.com

clinicaltrialsarena.com/news/senhwa-evaluate-pidnarulex-enhertu/

Senhwa to evaluate Pidnarulex and Enhertu in Phase Ib trial

Current HER2-targeted therapies have improved outcomes for breast and gastric cancers but have limited effectiveness in HER2-low solid tumours.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07137416

Study Details | NCT07137416 | Testing the Safety of the ...

This phase I trial tests the safety, side effects, and best dose of pidnarulex in combination with trastuzumab deruxtecan in treating patients with breast ...

3.

prnewswire.com

prnewswire.com/news-releases/senhwa-biosciences-aims-at-multi-billion-dollar-global-market-with-cx-5461-combined-with-adc-blockbuster-therapy-302649931.html

Senhwa Biosciences Aims at Multi-Billion Dollar Global ...

The study is designed for HER2-positive solid tumors and breast cancer patients, including those with HER2-low expression and metastatic breast ...

4.

insights.bio

insights.bio/bioconjugate-insights/journal/article/3718/industry-insights-converging-modalities-drive-the-next-wave-of-bioconjugate-therapies

Industry Insights: Converging modalities drive the next ...

Senhwa Biosciences announced that its first-in-class investigational agent pidnarulex (CX-5461) will be evaluated in combination with Enhertu in ...

5.

pharmabiz.com

pharmabiz.com/ArticleDetails.aspx?aid=183307&sid=2

Senhwa Biosciences aims at multi-billion dollar global ...

The study is designed for HER2-positive solid tumours and breast cancer patients, including those with HER2-low expression and metastatic breast ...

6.

trialx.com

trialx.com/clinical-trials/listings/325590/testing-the-safety-of/

Testing the Safety of the Combination of Anti-Cancer Drugs ...

This phase I trial tests the safety, side effects, and best dose of pidnarulex in combination with trastuzumab deruxtecan in treating patients ...

7.

cancernetwork.com

cancernetwork.com/view/fda-grants-fast-track-designation-to-pidnarulex-in-brca1-2-palb2-ovarian-and-breast-cancer

FDA Grants Fast Track Designation to Pidnarulex in ...

In previous phase 1 study, pidnarulex yielded clinically significant and lasting benefit for those with BRCA1/2- and PALB2-mutant disease, and ...

8.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07701

Testing How the Body Responds to the Drug CX-5461 ...

This phase I trial tests the safety, side effects, and best dose of pidnarulex (CX-5461) in treating patients with solid tumors that have spread from where ...