PYX-106 for Solid Tumors

Not currently recruiting at 21 trial locations

Overseen By Chalyse Bush

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pyxis Oncology, Inc

Must not be taking: Steroids, others

Disqualifiers: Brain metastases, Peripheral neuropathy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 19 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests PYX-106, a new treatment for solid tumors that have returned or stopped responding to standard treatments. The goal is to determine a safe and effective dose of PYX-106 for patients with certain types of cancer, such as lung, breast, and kidney cancer. Participants whose cancer has returned or progressed despite standard treatments and who have not responded to other care options may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have continuance of toxicities from prior anti-cancer agents that do not recover to Grade 1 before starting PYX-106 treatment, except for alopecia or endocrine deficiencies treated with stable hormone replacement therapy. It's best to discuss your current medications with the trial team.

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

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

Is there any evidence suggesting that PYX-106 is likely to be safe for humans?

Research has shown that PYX-106 is being tested for safety in individuals with solid tumors. So far, 33 participants have tried different doses to assess their tolerance. The ongoing studies aim to determine the optimal dose that is both safe and effective.

As the trial is in an early stage, the primary focus is on evaluating the safety of PYX-106 in humans. Researchers are closely monitoring for side effects and observing how the drug behaves in the body. Although specific safety data is not yet available, the continuation of the trial suggests no major safety issues have halted the study. This indicates that researchers are still gathering information to ensure its safety for a broader population. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about PYX-106 because it offers a potentially new way to tackle solid tumors. Unlike traditional treatments like chemotherapy and radiation, which target rapidly dividing cells indiscriminately, PYX-106 is designed to target specific pathways involved in tumor growth. This targeted approach not only aims to attack tumors more effectively but also could reduce the side effects typically associated with broader cancer treatments. By focusing on these unique pathways, PYX-106 has the potential to provide a more personalized and efficient treatment option for patients with solid tumors.

What evidence suggests that PYX-106 might be an effective treatment for solid tumors?

Research has shown that PYX-106 holds promise as a treatment for solid tumors. Early tests suggest it can help patients live longer without disease progression. In this trial, participants will receive escalating doses of PYX-106 to evaluate its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity. PYX-106 blocks a protein called Siglec-15, which can weaken the immune system's ability to fight cancer. By blocking this protein, PYX-106 may help the immune system attack cancer cells more effectively. Although data remains limited, initial findings are encouraging for its potential use in treating solid tumors. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with certain solid tumors that have stopped responding to standard treatments. They must have a measurable tumor, a life expectancy over 3 months, and be in good physical condition (ECOG 0 or 1). People can't join if they need high-dose steroids for brain metastases, haven't recovered from previous treatments' side effects, had major surgery recently, got live vaccines within the last month, or have other active cancers.

Inclusion Criteria

Life expectancy of >3 months, in the opinion of the Investigator

I am fully active or can carry out light work.

My cancer has returned or worsened despite treatment.

Exclusion Criteria

I have not received a live vaccine in the last 28 days.

I have moderate to severe nerve damage in my hands or feet.

I have had cancer before, but it was either treated successfully, is in remission for over 2 years, or is not expected to affect my survival within the next 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of PYX-106 to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity

19 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PYX-106

Trial Overview The study is testing PYX-106 to find the safest and most effective dose for treating various advanced solid tumors that no longer respond to conventional therapies. It's an early-phase trial primarily focused on dosage rather than comparing it with other treatments.

How Is the Trial Designed?

Group I: PYX-106 Dose Escalation Experimental Treatment 1 Intervention

Participants will receive escalating doses of PYX-106 to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of PYX-106, and to determine the recommended dose(s).

Who Is Running the Clinical Trial?

Pyxis Oncology, Inc

Lead Sponsor

Trials

4

Recruited

400+

Published Research Related to This Trial

In a study of 22 women with HER2-positive locally advanced breast cancer, the combination of pyrotinib and the TAC regimen resulted in a 100% objective response rate after neoadjuvant therapy, with 45.5% achieving a total pathological complete response (tpCR).

The treatment was generally well-tolerated, with most adverse events being mild (grade 1-2), although some patients experienced grade ≥3 side effects like diarrhea and rash, indicating an acceptable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant pyrotinib plus nab-paclitaxel, doxorubicin, and cyclophosphamide for HER2-positive locally advanced breast cancer: a retrospective case-series study. Yao, DS., Wang, W., Chang, JY., et al.[2022]

In a retrospective study of 25 patients with HER2-positive nonbreast advanced solid tumors, pyrotinib demonstrated promising antitumor activity, with a median progression-free survival (PFS) of 188 days and an overall survival (OS) of 250 days.

The treatment was generally well-tolerated, with diarrhea being the most common side effect (84% incidence), but only 12% of patients experienced severe (grade 3) diarrhea, indicating an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Study on the Efficacy and Safety of Pyrotinib-Based Therapy for HER2-Positive Nonbreast Advanced Solid Tumors. Wang, J., Zhang, B., Cheng, X., et al.[2022]

In a study of 100 patients with non-small-cell lung carcinoma receiving immunotherapy as a second-line treatment, the median progression-free survival (PFS) was 4 months and overall survival (OS) was 9 months, indicating that immunotherapy can be effective in this population.

The majority of patients (61%) experienced a partial response to treatment, suggesting that immunotherapy can lead to significant tumor reduction, although the specific drug used did not significantly impact overall survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of immunotherapy as second-line treatment and beyond in patients with advanced non-small-cell lung carcinoma. Rodríguez-Cid, JR., Chards, SC., González-Espinoza, IR., et al.[2022]

PARP inhibitors showed significantly better progression-free survival (PFS) compared to other maintenance therapies for advanced ovarian cancer, with hazard ratios ranging from 0.59 to 0.68 based on 16 trials.

Overall survival (OS) data for these therapies are still immature, indicating that while PFS is promising, more research is needed to fully understand long-term outcomes and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic literature review of efficacy and safety of first-line maintenance therapy trials in advanced ovarian cancer. Guy, H., Hawkes, C., Walder, L., et al.[2022]

Pyrotinib is an irreversible dual pan-ErbB receptor tyrosine kinase inhibitor that has received conditional approval in China for treating HER2-positive advanced breast cancer, specifically in patients who have already undergone anthracycline or taxane chemotherapy.

The approval was based on positive results from a phase II trial, highlighting its efficacy in combination with capecitabine for this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyrotinib: First Global Approval. Blair, HA.[2019]

In a pilot study involving 33 heavily pretreated patients with advanced cancers overexpressing ErbB1 and/or ErbB2, lapatinib showed preliminary evidence of clinical activity, with partial responses in 4 breast cancer patients and disease stabilization in 11 others.

Biomarker analysis indicated that clinical responses were associated with specific pretreatment levels of tumor markers and increased tumor cell apoptosis in responders, highlighting the need for further research to refine biomarkers for targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. Spector, NL., Xia, W., Burris, H., et al.[2018]

In a study involving 15 children with relapsed or refractory solid tumors, the combination of sorafenib and irinotecan was found to be well tolerated, with a recommended dosing regimen established for pediatric patients that resulted in prolonged disease stabilization.

Despite some dose-limiting toxicities observed, such as grade 3 diarrhea and thrombocytopenia, 60% of patients achieved stable disease, indicating that this oral outpatient treatment regimen is a feasible option for managing pediatric malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of sorafenib and irinotecan in pediatric patients with relapsed or refractory solid tumors. Meany, HJ., Widemann, BC., Hinds, PS., et al.[2023]

In a study of 29 patients with HER2-positive breast cancer brain metastasis, the combination of whole-brain radiotherapy (WBRT) and pyrotinib showed significant improvements in progression-free survival (6.5 months) and overall survival (15.5 months), indicating its efficacy in treating active brain metastasis.

Sequence treatment with WBRT, pyrotinib, and capecitabine was found to be more effective and less toxic than concurrent treatment, with a higher objective response rate (80.4% vs 58.6%), suggesting it may be the preferred approach for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyrotinib combining with radiotherapy on breast cancer with brain metastasis. Ma, X., Li, Y., Zhao, Z., et al.[2023]

Overall survival (OS) is the traditional measure of clinical benefit for cancer drugs, but it requires large studies and long follow-up times, making it less practical for assessing new treatments quickly.

Progression-free survival (PFS) and time to progression (TTP) are valuable alternative endpoints that directly measure the effects of treatments on cancer growth, and their improvement can indicate clinical benefit, potentially speeding up the development and availability of effective cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall survival: a gold standard in search of a surrogate: the value of progression-free survival and time to progression as end points of drug efficacy. Zhuang, SH., Xiu, L., Elsayed, YA.[2022]

In a meta-analysis of 26 trials involving 24,870 patients with epithelial ovarian cancer, the correlation between progression-free survival (PFS) and overall survival (OS) was found to be moderate (r2 = 0.52), indicating that PFS may not be a strong surrogate endpoint for OS.

The correlation between PFS and OS has weakened over time, particularly with the introduction of new treatment types, suggesting that while PFS is still relevant, its predictive value for OS is diminishing as more effective therapies become available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-free survival as a surrogate endpoint for overall survival in modern ovarian cancer trials: a meta-analysis. Sjoquist, KM., Lord, SJ., Friedlander, ML., et al.[2022]

Progression-free survival (PFS) is increasingly used as a primary endpoint in clinical trials for advanced breast and colorectal cancers, as it can be measured earlier than overall survival (OS) and is not affected by subsequent treatments.

While PFS has not been validated as a surrogate for OS in advanced breast cancer, it is considered a valid surrogate in advanced colorectal cancer after first-line chemotherapy, highlighting the need for careful endpoint selection in cancer trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-free survival as surrogate and as true end point: insights from the breast and colorectal cancer literature. Saad, ED., Katz, A., Hoff, PM., et al.[2022]

In a Phase II study involving 49 patients with advanced cervical cancer, intravenous topotecan showed moderate activity with an overall response rate of 18.6%, indicating some effectiveness in treating this difficult condition.

However, the treatment was associated with significant hematologic toxicity, with 68% of patients experiencing grade 4 neutropenia and 18% grade 4 thrombocytopenia, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study. Muderspach, LI., Blessing, JA., Levenback, C., et al.[2022]

In a phase I study involving 17 patients, the combination of sorafenib and vorinostat was found to be poorly tolerated in patients with advanced renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC), leading to dose reductions and interruptions due to side effects like hand-foot syndrome.

While no confirmed responses were observed, some patients with RCC experienced minor responses, suggesting that lower doses may be necessary for better tolerability and potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of sorafenib and vorinostat in patients with advanced solid tumors with expanded cohorts in renal cell carcinoma and non-small cell lung cancer. Dasari, A., Gore, L., Messersmith, WA., et al.[2021]

In a study of 44 patients with stage II-III HER2-positive breast cancer, the combination of epirubicin and cyclophosphamide with pyrotinib achieved a high objective response rate of 97.3%, indicating strong efficacy in the neoadjuvant setting.

The treatment was generally safe, with manageable side effects; however, 88.6% of patients experienced diarrhea, and 9.1% had severe leukopenia, suggesting that while effective, monitoring for adverse events is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of epirubicin and cyclophosphamide combined with pyrotinib in neoadjuvant treatment for HER2-positive breast cancer: A real-world study. Li, F., Liang, Y., Luo, M., et al.[2023]

In a comprehensive analysis of 24 randomized trials involving 20,438 patients with metastatic colorectal cancer, progression-free survival (PFS) was found to be strongly correlated with overall survival (OS), indicating that PFS is a valid surrogate endpoint for OS in current treatment regimens.

The study showed that the correlation between PFS and OS was particularly strong in trials using targeted therapies in combination with chemotherapy, reinforcing the importance of PFS as a measure of treatment efficacy in metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of progression-free survival as a surrogate endpoint for survival in chemotherapy and targeted agent metastatic colorectal cancer trials. Sidhu, R., Rong, A., Dahlberg, S.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05718557?term=AREA%5BNCTIdSearch%5D(NCT05718557)&rank=1

Study of PYX-106 in Solid Tumors Most clinical studies have one primary outcome measure, but some have more than one. ... The main reason for the clinical trial. The types of primary purpose are: ...

2. ir.pyxisoncology.com ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-announces-portfolio-prioritization-focusing

Pyxis Oncology Announces Portfolio Prioritization ... To date, the Phase 1 monotherapy trial of PYX-106 enrolled 45 patients with advanced solid tumors. PYX-106 was observed as generally safe ...

3. withpower.com withpower.com/trial/phase-1-neoplasms-1-2023-0992f

PYX-106 for Solid Tumors · Info for Participants What data supports the effectiveness of the drug PYX-106 for solid tumors? The research suggests that progression-free survival (PFS), which measures how ...

4. biosion.com biosion.com/news/datail/648297ec3faa391e8e639197

About PYX-106-101 PYX-106-101 (NCT05718557) is an open-label, multicenter, Phase 1 dose escalation trial designed to evaluate the safety, tolerability, pharmacokinetics, ...

5. researchgate.net researchgate.net/publication/385584950_567_PYX-106_a_highly_differentiated_anti-Siglec-15_monoclonal_antibody_reverses_Siglec-15_mediated_immune_suppression_and_enhances_cytotoxic_activity_in_human_lymphocytes

(PDF) 567 PYX-106, a highly differentiated anti-Siglec-15 ... Remarkably, long-term anti-tumor efficacy of PYX-201 was observed as tumors did not relapse even after >100 days in a breast cancer PDX model.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05718557

NCT05718557 | Study of PYX-106 in Solid Tumors Participants will receive escalating doses of PYX-106 to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor ...

7. ir.pyxisoncology.com ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-provides-corporate-update-and-reports-financial-1/

Pyxis Oncology Provides Corporate Update and Reports ... Dose escalation of PYX-106 and safety monitoring is ongoing with 33 subjects dosed to date in the Phase 1 trial. The Company expects to report preliminary data ...

8. sec.gov sec.gov/Archives/edgar/data/0001782223/000095017024097054/pyxs-ex99_1.htm

EX-99.1 Dose escalation of PYX-106 and safety monitoring is ongoing with 33 subjects dosed to date in the Phase 1 trial. •. The Company expects to report preliminary ...

9. clin.larvol.com clin.larvol.com/trial-detail/NCT05718557

Study of PYX-106 in Solid Tumors Dose escalation of PYX-106 and safety monitoring is ongoing with 33 subjects dosed to date in the Phase 1 trial. The Company expects to report preliminary data ...