PYX-106 for Solid Tumors

Recruiting at 20 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

47 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to determine the recommended dose(s) of PYX-106 in participants with relapsed/refractory solid tumors.

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.

What data supports the idea that PYX-106 for Solid Tumors is an effective treatment?

The available research shows that progression-free survival (PFS) is often used as an early indicator of a treatment's effectiveness in cancer trials. While the specific data on PYX-106 for Solid Tumors is not provided, studies in similar cancer treatments suggest that improvements in PFS are strongly linked to better overall survival (OS). This means that if PYX-106 improves PFS, it might also lead to longer survival for patients. However, without direct data on PYX-106, we can't make a definitive comparison to other treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the drug PYX-106 for solid tumors?

The research suggests that progression-free survival (PFS), which measures how long a patient lives without the cancer getting worse, is a good indicator of overall survival (OS) in cancer treatments. This means that if PYX-106 improves PFS, it might also improve overall survival, making it potentially effective for treating solid tumors. ^{1 2 3 4 5}

What existing safety data is available for PYX-106 in solid tumors?

The provided research does not contain specific safety data for PYX-106 or any treatment under that name. The studies mentioned focus on other treatments such as topotecan, lapatinib, sorafenib, irinotecan, and vorinostat, none of which are identified as PYX-106. Therefore, no safety data for PYX-106 is available in the provided research. ^{6 7 8 9 10}

Is the drug PYX-106 a promising treatment for solid tumors?

The information provided does not mention PYX-106 specifically, so we cannot determine if it is a promising treatment for solid tumors based on the given articles. ^{11 12 13 14 15}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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 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]

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 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]

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 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]

References

1. United States 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. [2022]

2. England 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. [2022]

3. United States 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Progression-free survival as a surrogate endpoint for overall survival in modern ovarian cancer trials: a meta-analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Progression-free survival as surrogate and as true end point: insights from the breast and colorectal cancer literature. [2022]

6. United States 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. [2022]

7. United States 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. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Systematic literature review of efficacy and safety of first-line maintenance therapy trials in advanced ovarian cancer. [2022]

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

Phase 1 study of sorafenib and irinotecan in pediatric patients with relapsed or refractory solid tumors. [2023]

10. United States 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. [2021]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Pyrotinib: First Global Approval. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Pyrotinib combining with radiotherapy on breast cancer with brain metastasis. [2023]

13. Switzerland 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. [2023]

14. China (Republic : 1949- ) 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. [2022]

15. Egypt pubmed.ncbi.nlm.nih.gov

Retrospective Study on the Efficacy and Safety of Pyrotinib-Based Therapy for HER2-Positive Nonbreast Advanced Solid Tumors. [2022]