PYX-201 for Solid Tumors

Recruiting in Palo Alto (17 mi)

+18 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Pyxis Oncology, Inc

Disqualifiers: Brain metastases, Cardiovascular disease, Active infections, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing PYX-201, a new drug, to find the best dose for patients whose solid tumors have returned or didn't respond to other treatments. The drug aims to either kill cancer cells or boost the immune system to fight the cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have received systemic anticancer therapy within 28 days or within 5 half-lives before starting the study drug.

What data supports the effectiveness of the drug PYX-201 for solid tumors?

While there is no direct data on PYX-201, similar drugs like pyrotinib, which is also a tyrosine kinase inhibitor (a type of drug that blocks certain proteins involved in cancer cell growth), have shown effectiveness in treating HER2-positive breast cancer when combined with other treatments. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

Adults over 18 with certain types of advanced solid tumors, like lung or breast cancer, who've seen their disease get worse after treatment can join. They should be fairly active (ECOG 0-1), have a life expectancy over 3 months, and provide tumor samples. People with brain metastases needing high-dose steroids or recent major surgery can't participate.

Inclusion Criteria

I have at least one tumor that can be measured or I have breast cancer that has spread to bones only.

I am fully active or can carry out light work.

Life expectancy of >3 months

Exclusion Criteria

I do not have an active infection needing treatment as I start PYX-201.

I had cancer before, but it's either completely treated or in remission for over 2 years.

I have not had major surgery in the last 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of PYX-201 as an IV infusion to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity

3 weeks

Multiple visits (in-person)

Cohort Treatment

Participants in various cohorts receive PYX-201 as an IV infusion at the recommended dose

Up to approximately 2 years

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PYX-201 (Other)

Trial Overview The trial is testing different doses of PYX-201 to find the safest and most effective amount for treating various advanced solid tumors in patients whose previous treatments didn't work.

Participant Groups

Group I: Part 2: Cohort D Experimental Treatment 1 Intervention

Participants with various advanced solid tumor types, including non-small cell lung cancer (NSCLC), sarcomas, rare solid tumor head and neck (H\&N) cancers, ovarian cancer (OVCA), cervical cancer, and endometrial cancer, will receive PYX-201 as an IV infusion at the recommended dose for Part 2.

Group II: Part 2: Cohort C Experimental Treatment 1 Intervention

Participants with hormone receptor (HR)-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative (immunohistochemistry \[IHC\] 0, IHC 1+, or IHC 2+/in situ hybridization \[ISH\]-negative) breast cancer who had progressed on cyclin-dependent kinase 4/6 (CDK-4/6) inhibitors plus endocrine therapy and one line of chemotherapy, and had received no more than three prior lines of systemic therapy, will receive PYX-201 as an IV infusion at the recommended dose for Part 2.

Group III: Part 2: Cohort B Experimental Treatment 1 Intervention

Participants with triple-negative breast cancer (TNBC) who have been treated with at least one but no more than two lines of prior systemic therapy will receive PYX-201 as an IV infusion at the recommended dose for Part 2.

Group IV: Part 2: Cohort A Experimental Treatment 1 Intervention

Participants with recurrent, persistent, and/or metastatic head and neck squamous cell carcinoma (HNSCC) who have received at least one but no more than two lines of prior systemic therapy, including platinum-based therapy and a programmed cell death protein 1 (PD-1) inhibitor, and participants who have received up to two lines of prior therapy that must include one prior PD-1 inhibitor and one prior epidermal growth factor receptor (EGFR)-directed treatment, will receive PYX-201 as an IV infusion at the recommended dose for Part 2.

Group V: Part 1: PYX-201 Dose Escalation Experimental Treatment 1 Intervention

Participants will receive escalating doses of PYX-201 as an intravenous (IV) infusion to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of PYX-201. Intra-participant dose escalation may be considered for participants who have adequately tolerated therapy.

Who Is Running the Clinical Trial?

Pyxis Oncology, Inc

Lead Sponsor

Trials

4

Recruited

400+

Findings from Research

A 37-year-old woman with HER2-positive advanced breast cancer showed a significant clinical response after treatment with a combination of pyrotinib, trastuzumab, paclitaxel, and cisplatin, achieving a clinical partial response after 4 cycles.

The patient underwent surgery and achieved a pathologic complete response, indicating that the combination therapy with pyrotinib can dramatically improve outcomes in patients with aggressive HER2-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological Complete Response from Pyrotinib Combined with Trastuzumab, Paclitaxel and Cisplatin in a Postpartum Woman with HER2-Positive Locally Advanced Breast Cancer: A Case Report. He, L., Zhang, F., Ma, Y., et al.[2022]

In a phase II trial involving 20 female patients with HER2-positive operable and locally advanced breast cancer, the combination of pyrotinib with chemotherapy showed a total pathological complete response (tpCR) rate of 73.7%, indicating high efficacy in this treatment setting.

The treatment was generally safe, with the most common side effects being diarrhea and leukopenia in 90% of patients, but no severe (grade 5) adverse events were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Pyrotinib plus Trastuzumab and Chemotherapy for Stage I-III HER2-Positive Breast Cancer: A Phase II Clinical Trial. Xuhong, J., Qi, X., Tang, P., et al.[2022]

Patients with non-small-cell lung cancer (NSCLC) who have EGFR activating mutations experience significantly longer progression-free survival (PFS) when treated with EGFR tyrosine-kinase inhibitors (TKIs) like erlotinib (12.4 months) and gefitinib (9.4 months) compared to chemotherapy (5.6 months).

The analysis included data from 27 studies on erlotinib (731 patients) and 54 studies on gefitinib (1802 patients), demonstrating a clear advantage of TKIs over chemotherapy in extending PFS for EGFR mutation-positive NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled analysis of clinical outcome for EGFR TKI-treated patients with EGFR mutation-positive NSCLC. Paz-Ares, L., Soulières, D., Moecks, J., et al.[2021]

In a study of 212 patients with metastatic breast cancer, the addition of bevacizumab to chemotherapy significantly prolonged progression-free survival (PFS) to 9.3 months compared to 7.6 months for chemotherapy alone, and overall survival (OS) to 28.9 months compared to 22.6 months.

Patients who developed hypertension during treatment with bevacizumab had a notably better outcome, with a PFS of 13.7 months and a 2-year OS rate of 78%, suggesting that hypertension may be a marker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypertension as a predictive marker for bevacizumab in metastatic breast cancer: results from a retrospective matched-pair analysis. Gampenrieder, SP., Romeder, F., Muß, C., et al.[2022]

References

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

Pathological Complete Response from Pyrotinib Combined with Trastuzumab, Paclitaxel and Cisplatin in a Postpartum Woman with HER2-Positive Locally Advanced Breast Cancer: A Case Report. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant Pyrotinib plus Trastuzumab and Chemotherapy for Stage I-III HER2-Positive Breast Cancer: A Phase II Clinical Trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pooled analysis of clinical outcome for EGFR TKI-treated patients with EGFR mutation-positive NSCLC. [2021]

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

I-SPY2 platform: New lessons from the olaparib and durvalumab combination in breast cancer treatment. [2021]

5. Greece pubmed.ncbi.nlm.nih.gov

Hypertension as a predictive marker for bevacizumab in metastatic breast cancer: results from a retrospective matched-pair analysis. [2022]