HF158K1 for HER-2 Positive Solid Cancers

Recruiting at 2 trial locations

Overseen By Yongfeng Huang

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: HighField Biopharmaceuticals Corporation

Must not be taking: CYP3A4 inhibitors, CYP2D6 inducers

Disqualifiers: Cardiovascular diseases, Brain metastases, others

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

Compensation: Varies

Number of Visits: 3

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called HF158K1 for individuals with HER-2 positive solid cancers that haven't responded to other treatments. The trial aims to determine the right dose and assess the safety of HF158K1, a chemotherapy that targets cancer cells more precisely. Participants will receive varying doses to identify the most effective one with the fewest side effects. This trial may suit those with advanced cancer that hasn't improved with standard treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, specifically those that strongly inhibit or induce CYP3A4, CYP2D6, or P-gp, at least one week before starting the study. Additionally, participants must not have received certain cancer treatments within a specified time before the trial.

Is there any evidence suggesting that HF158K1 is likely to be safe for humans?

Research shows that HF158K1 is an experimental treatment combining doxorubicin hydrochloride, a well-known cancer drug, with a special delivery system. This system targets HER2-positive cancer cells, often found in certain types of breast cancer.

Doxorubicin, the main ingredient in HF158K1, is effective but can cause serious side effects at high doses, such as heart damage and low blood cell counts. Delivering the drug directly to cancer cells using a liposome (a tiny fat bubble) may help reduce these risks.

Safety data for similar treatments using liposomal doxorubicin suggest they are generally well-tolerated, with side effects similar to traditional doxorubicin, but sometimes less severe. Common side effects include nausea, tiredness, and low blood counts.

HF158K1 is in an early testing phase, focusing on finding the safest dose. While the treatment is new, its components are based on drugs that doctors have used for a long time. This provides some confidence in its potential safety, though more data from ongoing trials will give clearer answers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about HF158K1 for HER-2 positive solid cancers because it offers a potentially new approach to treatment by targeting the HER-2 protein. Unlike the standard treatments, such as monoclonal antibodies and tyrosine kinase inhibitors, HF158K1 might work differently, possibly leading to improved outcomes. Another exciting aspect is its dose escalation strategy, which aims to find the most effective and safest dosage quickly. This innovative approach could mean more personalized treatment options for patients with HER-2 positive cancers.

What evidence suggests that HF158K1 might be an effective treatment for HER-2 positive solid cancers?

Research shows that HF158K1 is designed to treat HER2-positive cancers. This trial will explore different dosages of HF158K1, which uses a special system to deliver the cancer-fighting drug doxorubicin directly to tumor cells with the HER2 marker. Doxorubicin is a strong drug known for fighting cancer, but it can have side effects. By using a targeted method with liposomes (tiny fat bubbles), HF158K1 aims to reduce these side effects and improve effectiveness. Early studies suggest that this targeted delivery can effectively attach to and attack HER2-positive tumor cells, potentially leading to better outcomes for patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Minal Barve, MD

Principal Investigator

Mary Crowley Cancer Research

Are You a Good Fit for This Trial?

Adults with advanced solid tumors expressing HER-2 who have not responded to standard treatments or for whom no treatment is available. They must be in relatively good health, with proper organ and bone marrow function, and willing to use contraception. Excluded are those with certain heart conditions, uncontrolled blood pressure, recent major surgeries or serious infections, prior high-dose doxorubicin treatment, brain metastases causing symptoms, or known allergies to similar drugs.

Inclusion Criteria

My blood, liver, and kidney tests are within normal ranges.

Voluntary to participate in the clinical study, sign a written informed consent form, and able to comply with clinical visits and study-related procedures

Expected survival of at least 3 months

Exclusion Criteria

Known allergy to specific compounds or excipients

I have received a high dose of doxorubicin or experienced severe heart issues from it.

I haven't taken certain medications recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1a will assess the safety, tolerability, and pharmacokinetics of HF158K1 to determine the maximum tolerated dose through the incidence of dose-limiting toxicity.

21 days per cycle

Visits on Day 1, 8, 15 of each cycle

Dose Expansion

Phase 1b will assess safety and preliminary efficacy of HF158K1 in participants with specific tumor types in selected dose groups.

21 days per cycle

Visits on Day 1, 8, 15 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) at the end of treatment

What Are the Treatments Tested in This Trial?

Interventions

• HF158K1

Trial Overview The trial tests different doses of HF158K1—a liposome form of doxorubicin combined with a HER2-targeting component—in patients with varying levels of HER-2 expression in their tumors. The goal is to assess the drug's safety profile and preliminary effectiveness at these doses.

How Is the Trial Designed?

Group I: Dose escalation cohort 1: HF158K1 given Q3W at 60 mg/m² Experimental Treatment 1 Intervention

Participants in this dose group(60 mg/m²) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.

Group II: Dose escalation cohort 1: HF158K1 given Q3W at 6 mg/m² Experimental Treatment 1 Intervention

Participants in this dose group(6 mg/m²) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.

Group III: Dose escalation cohort 1: HF158K1 given Q3W at 45 mg/m² Experimental Treatment 1 Intervention

Participants in this dose group(45 mg/m²) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.

Group IV: Dose escalation cohort 1: HF158K1 given Q3W at 30 mg/m² Experimental Treatment 1 Intervention

Participants in this dose group(30 mg/m²) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.

Group V: Dose escalation cohort 1: HF158K1 given Q3W at 2 mg/m² Experimental Treatment 1 Intervention

Participants in this dose group(2 mg/m²) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.

Group VI: Dose escalation cohort 1: HF158K1 given Q3W at 15 mg/m² Experimental Treatment 1 Intervention

Participants in this dose group(15 mg/m²) will receive HF158K1 on D1 of each treatment cycle (3 weeks as a treatment cycle) through intravenous infusion.

Who Is Running the Clinical Trial?

HighField Biopharmaceuticals Corporation

Lead Sponsor

Trials

4

Recruited

160+

Published Research Related to This Trial

The maximum tolerated dose (MTD) for liposome-encapsulated doxorubicin citrate (LD) and docetaxel in breast cancer patients was established at 50 mg/m² and 60 mg/m², respectively, with manageable dose-limiting toxicities including diarrhea and fatigue.

The treatment resulted in a promising pathologic complete response rate of 44% in the patients, with no significant interruptions due to cardiac toxicity despite some decline in left ventricular ejection fraction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neo-adjuvant treatment in stages II and IIIA, HER2-overexpressing breast cancer patients. GEICAM 2003-03 study. Antón, A., Ruiz, A., Seguí, MA., et al.[2020]

In a study of 67 patients with metastatic breast cancer, the combination of liposome-encapsulated doxorubicin (TLC D-99) and cyclophosphamide (CTX) resulted in a 64% overall response rate, demonstrating significant efficacy as a first-line treatment.

The treatment was generally well tolerated, with mild non-hematological toxicities and only one case of cardiac toxicity, suggesting that TLC D-99 may offer a safer alternative to conventional doxorubicin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal-encapsulated doxorubicin plus cyclophosphamide as first-line therapy in metastatic breast cancer: a phase II multicentric study. Giotta, F., Lorusso, V., Maiello, E., et al.[2020]

The novel tri-functional immunoliposomes (TFIL) effectively target HER2-positive breast cancer cells and engage T-lymphocytes, demonstrating complete cytotoxicity against these cancer cells in vitro, which suggests a promising mechanism for enhancing treatment efficacy.

TFIL showed superior performance compared to traditional treatments, with high drug loading efficiency and stability, indicating potential for improved clinical outcomes while addressing issues of treatment resistance and cardiotoxicity associated with trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Evaluation of Tri-Functional Immunoliposomes for the Treatment of HER2 Positive Breast Cancer. Vaidya, T., Straubinger, RM., Ait-Oudhia, S.[2019]

Anti-p185HER2 immunoliposomes, which are designed to target breast cancer cells overexpressing the HER2 protein, show high-affinity binding and enhanced antiproliferative effects compared to free antibody fragments, indicating improved therapeutic potential.

In vivo studies in Scid mice with human breast tumor xenografts demonstrate that these immunoliposomes can effectively deliver the chemotherapy drug doxorubicin directly to tumors, suggesting they could be a promising treatment option for HER2-overexpressing cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of anti-p185HER2 immunoliposomes for cancer therapy. Park, JW., Hong, K., Carter, P., et al.[2020]

In a phase 1 clinical study involving 29 patients with advanced solid tumors, anti-EGFR immunoliposomes loaded with doxorubicin were well tolerated up to a maximum dose of 50 mg/m², with only mild side effects observed at lower doses.

The treatment showed clinical activity, including one complete response and one partial response, suggesting that further investigation in phase 2 trials is warranted due to its potential efficacy in targeting EGFR-overexpressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti-EGFR immunoliposomes in advanced solid tumours: a phase 1 dose-escalation study. Mamot, C., Ritschard, R., Wicki, A., et al.[2022]

Anti-HER2 immunoliposomes (ILs) effectively target HER2-overexpressing cancers, showing efficient tumor localization and penetration, which is significantly better than non-targeted liposomes.

Doxorubicin-loaded anti-HER2 ILs demonstrated increased antitumor effectiveness and reduced systemic toxicity compared to free doxorubicin, highlighting their potential as a safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-HER2 immunoliposomes for targeted therapy of human tumors. Park, JW., Hong, K., Kirpotin, DB., et al.[2019]

The study developed an aptamer-labeled liposomal nanoparticle system that effectively delivers doxorubicin specifically to Her-2+ breast cancer cells, achieving a high drug encapsulation efficiency of approximately 93%.

The targeted delivery system (formulation F5) significantly increased the uptake of doxorubicin in Her-2+ cancer cells by over 60% compared to non-targeted nanoparticles, leading to improved cytotoxicity against these cancer cells and potentially reducing the required dose of doxorubicin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Delivery of Doxorubicin Liposomes for Her-2+ Breast Cancer Treatment. Chowdhury, N., Chaudhry, S., Hall, N., et al.[2022]

In a study of 52 patients with advanced breast cancer, high-dose liposome-encapsulated doxorubicin (TLC D-99) showed an overall response rate of 46%, but the treatment was associated with significant cardiotoxicity, including symptomatic congestive heart failure in 13% of patients.

The high rate of severe side effects, particularly cardiac issues linked to prior doxorubicin treatment and cumulative doses of TLC D-99, suggests that the current dosing regimen does not provide sufficient therapeutic benefit to justify further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of high-dose liposome-encapsulated doxorubicin with granulocyte colony-stimulating factor in metastatic breast cancer. TLC D-99 Study Group. Shapiro, CL., Ervin, T., Welles, L., et al.[2017]

In a study involving 69 women with HER-2-overexpressing locally advanced and metastatic breast cancer, the combination of nonpegylated liposomal doxorubicin, paclitaxel, and trastuzumab showed a remarkable overall response rate of 98.1%, indicating high efficacy in treating this type of cancer.

The treatment was found to be safe, with only 17% of patients experiencing asymptomatic declines in heart function, and no cases of symptomatic heart failure, suggesting that the combination does not pose significant cardiac risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase I/II study. Cortes, J., Di Cosimo, S., Climent, MA., et al.[2022]

The chemotherapy regimen using liposome-encapsulated doxorubicin (TLC D-99), fluorouracil, and cyclophosphamide showed a high overall response rate of 73% in 41 women with metastatic breast cancer, with a median overall survival of 19.4 months.

Despite administering high cumulative doses of doxorubicin, the treatment was associated with low cardiac toxicity, with only 7% of patients experiencing protocol-defined cardiac issues, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of liposome-encapsulated doxorubicin, cyclophosphamide, and fluorouracil as first-line therapy in patients with metastatic breast cancer. Valero, V., Buzdar, AU., Theriault, RL., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05861895

NCT05861895 | A Clinical Study to Investigate the Safety, ... HF158K1 contains multiple copies of the targeting antibody on liposome surface. It is designed to bind and deliver the chemotherapeutic doxorubicin to tumor ...

2. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/her2-targeted-liposomal-doxorubicin-hydrochloride-hf158k1

HER2-targeted liposomal doxorubicin hydrochloride ... Upon administration of HER2-targeted liposomal doxorubicin HCl HF158K1, the immunoliposome targets and binds to HER2-expressing tumor cells, thereby allowing ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10054554/

Recent Preclinical and Clinical Progress in Liposomal ... Doxorubicin (DOX) is a potent anti-cancer agent that has garnered great interest in research due to its high efficacy despite dose-limiting toxicities.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666845925000601

Advancing liposomal doxorubicin for targeted cancer therapy This review systematically analyzes the development of liposome-based formulations for DOX, from early advancements to next-generation functionalized ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7995642/

Targeted Delivery of Doxorubicin Liposomes for Her-2 ... The goal of this study is to enhance the delivery of doxorubicin by formulating an aptamer-labeled liposomal nanoparticle delivery system.

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05861895/a-clinical-study-to-investigate-the-safety-tolerability-pharmacokinetics-immunogenicity-and-preliminary-efficacy-of-hf158k1-in-participants-with-her-2-positive-or-her-2-low-expression-advanced-solid-tumors

A Clinical Study to Investigate the Safety, Tolerability ... HF158K1 is an investigational liposome form of doxorubicin hydrochloride, an anthracycline topoisomerase inhibitor, encapsulated by lipid ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/208657Orig1s000.pdf

ANDA 208657 - accessdata.fda.gov The safety data reflect exposure to doxorubicin hydrochloride liposome injection in 1310 patients including: 239 patients with ovarian ...