PM54 for Solid Tumors

Recruiting at 2 trial locations

Overseen By Gaston Federico Boggio, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: PharmaMar

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Uncontrolled hypertension, Active infection, HIV, others

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

Compensation: Varies

Number of Visits: 1

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, PM54, for individuals with advanced solid tumors, such as certain types of lung, breast, or skin cancer. The main goal is to assess the safety of PM54 and determine the appropriate dose. The trial will also evaluate the drug's effectiveness against these cancers. Eligible participants have previously tried standard treatments and experienced cancer progression. 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 drug.

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

The trial protocol does not specify if you need to stop all current medications, but there are specific washout periods for certain treatments. You must stop chemotherapy at least three weeks before, monoclonal antibody therapy four weeks before, and other biological therapies two weeks before starting the trial. Hormonal therapies for hormone-sensitive breast cancer must be stopped at least one week before, except for certain exceptions.

Is there any evidence suggesting that PM54 is likely to be safe for humans?

Researchers are currently studying PM54 to assess its safety and tolerability. They aim to determine the highest dose patients can take without serious side effects. As PM54 is in early testing stages, limited information exists about its safety in humans. This phase seeks to identify major safety issues and understand how the body processes the treatment. Researchers gradually increase the dose to find the maximum safe amount. If PM54 proves safe and well-tolerated by the end of these studies, it will undergo further testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about PM54 because it represents a new approach to treating solid tumors. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, PM54 is designed to target specific pathways involved in tumor growth. This targeted approach not only aims to enhance effectiveness but also potentially reduces side effects compared to current options. Additionally, PM54 is administered intravenously, allowing for direct delivery into the bloodstream, which may help in achieving optimal therapeutic levels quickly.

What evidence suggests that PM54 might be an effective treatment for solid tumors?

Research has shown that PM54, the treatment tested in this trial for advanced solid tumors, appears promising in early studies. Lab results suggest that PM54 effectively slows the growth and spread of cancer cells and prevents them from dividing. Although human studies have provided limited information, these early signs offer hope for its potential effectiveness. Further research is needed to confirm these findings in larger groups. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced solid tumors, including specific cancers of the urinary tract, skin (melanoma), gastrointestinal system, lung, gynecological organs, breast and certain sarcomas. Participants must be in fairly good health otherwise (ECOG ≤1).

Inclusion Criteria

I have an advanced solid tumor with no standard treatment options.

Voluntarily signed and dated written informed consent obtained prior to any specific study procedure

Laboratory values within seven days prior to first infusion must meet specified criteria

Exclusion Criteria

I do not have major illnesses or conditions that would interfere with the treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ia - Dose Escalation

Evaluate the safety, tolerability, and identify dose-limiting toxicities (DLTs) of PM54

3 weeks

Cycle 1 is 21 days

Phase Ib - Expansion

Evaluate the antitumor activity of PM54 in terms of clinical benefit and response

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• PM54

Trial Overview PM54's safety and maximum tolerated dose are being tested first. Then its effectiveness against tumor growth will be assessed using imaging criteria (RECIST v.1.1) or serum markers in patients with selected advanced solid tumors.

How Is the Trial Designed?

Group I: PM54 Experimental Treatment 1 Intervention

Phase Ia (dose escalation) stage: Patients will receive PM54 i.v. at a starting dose of 0.3 mg/m2. Phase Ib (safety run-in) stage: The maximum tolerated dose (MTD) of PM54 previously defined in Phase Ia will be reassessed. Phase Ib (expansion) stage: Patients will receive PM54 i.v. at the recommended dose selected after the safety run-in stage.

Who Is Running the Clinical Trial?

PharmaMar

Lead Sponsor

Trials

93

Recruited

11,800+

José María Fernández de Sousa-Faro

PharmaMar

Chief Executive Officer since 1986

PhD in Biochemistry, Complutense University of Madrid

Carmen Cuevas Marchante

PharmaMar

Chief Medical Officer since 2002

MD, University of Navarra

Published Research Related to This Trial

Immune checkpoint inhibitors, like ipilimumab, nivolumab, and pembrolizumab, are currently approved for use in the adjuvant setting only for surgically resected melanoma, but their potential is being explored in other solid tumors.

Ongoing trials are showing promising preliminary results for the use of these inhibitors in various cancers, including lung, head and neck, bladder, and renal cell carcinomas, as well as emerging data for esophageal and colorectal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging use of immune checkpoint blockade in the adjuvant setting for solid tumors: a review. Moujaess, E., Haddad, FG., Eid, R., et al.[2020]

In a study of 62 patients with stage IIIB-IV non-small cell lung cancer, combining MVP chemotherapy with concurrent radiotherapy resulted in a significantly higher response rate (48.4% vs. 19.4%) and improved 1-year survival rate (54.8% vs. 22.6%) compared to MVP chemotherapy alone.

While the combination treatment was more effective, it also led to a higher incidence of grade II-III leukopenia, indicating a need for careful monitoring of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of MVP chemotherapy combined with concurrent radiotherapy for advanced non-small cell lung cancer]. Qiao, T., Zhou, D., Chen, W., et al.[2011]

A meta-analysis of nine trials with 1190 patients showed that platinum-based chemotherapy provides a survival benefit for patients with advanced non-small cell lung cancer compared to best supportive care.

Recent studies indicate that newer agents like paclitaxel and docetaxel, when combined with platinum-based regimens, offer modest improvements in survival and quality of life, but no single combination has been found superior in terms of survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic chemotherapy in advanced non-small cell lung cancer: a review of standard treatment paradigms. Socinski, MA.[2015]

Chemotherapy, typically involving cisplatin or carboplatin combined with a third-generation cytotoxic agent, is the standard treatment for patients with metastatic non-small cell lung cancer who have a good performance score, with a recommended duration of at least 3 to 4 cycles unless the disease progresses.

For older patients over 70 with a good performance score, chemotherapy remains the standard treatment, although the specific regimen is still uncertain; this approach aims to enhance survival and quality of life, especially for those experiencing tumor relapse or disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for metastased non-small cell lung cancer]. Groen, HJ., Smit, EF., Sleijfer, DT.[2013]

In a study of 292 patients with advanced urothelial cancer, a high neutrophil-to-lymphocyte ratio (NLR) both before and during chemotherapy was linked to significantly shorter progression-free and overall survival times, indicating its role as a predictor of poor outcomes.

Specifically, patients with a persistent NLR greater than 3 had a median progression-free survival of only 3.2 months and overall survival of 5.7 months, highlighting the importance of monitoring NLR as a potential biomarker for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High neutrophil-to-lymphocyte ratio persistent during first-line chemotherapy predicts poor clinical outcome in patients with advanced urothelial cancer. Rossi, L., Santoni, M., Crabb, SJ., et al.[2022]

In a study of 155 patients with advanced solid tumors, those with a better performance status (ECOG PS 0-1) had a median overall survival (OS) of 9.1 months, compared to only 2.9 months for those with poorer performance status (ECOG PS 2-4), indicating that performance status significantly impacts treatment outcomes with immune checkpoint inhibitors (ICIs).

Despite having a poor performance status, 27.3% of patients in the study were still alive after one year, and the treatment was generally well-tolerated, with 84.6% of patients experiencing no severe toxicities, suggesting that ICIs can be a safe and effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. Kapoor, A., Noronha, V., Patil, VM., et al.[2023]

In 2016, the FDA approved three new drugs for solid tumors: olaratumab for soft-tissue sarcoma, atezolizumab for bladder cancer, and rucaparib for ovarian cancer, highlighting advancements in targeted therapies and immunotherapies.

The year also saw the expansion of previously approved drugs into 11 new patient populations, emphasizing the need for oncologists to understand the mechanisms and potential toxicities of both new and existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel and Expanded Oncology Drug Approvals of 2016-PART 1: New Options in Solid Tumor Management. Knepper, TC., Saller, J., Walko, CM.[2021]

Immunotherapy, particularly immune checkpoint inhibitors, has significantly improved treatment outcomes for high-risk resectable and metastatic melanoma, showcasing its effectiveness across various cancer types.

The success of immunotherapy in melanoma has led to its approval and evaluation in other solid tumors, indicating a broader application of these therapies in both early and advanced stages of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Landscape of Immune Checkpoint Inhibition for Solid Malignancies. Keung, EZ., Wargo, JA.[2020]

In a study of 187 patients with non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, those with PD-L1 levels of 90%-100% showed significantly better treatment outcomes with pembrolizumab, including a higher overall response rate (60% vs. 32.7%) and longer median progression-free survival (14.5 months vs. 4.1 months).

Patients with higher PD-L1 expression not only had improved response rates but also longer overall survival, indicating that PD-L1 levels can be a critical factor in predicting the efficacy of pembrolizumab as a first-line treatment for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Aguilar, EJ., Ricciuti, B., Gainor, JF., et al.[2023]

Chemotherapy has been shown to improve survival and quality of life in patients with advanced non-small cell lung cancer, including those with poor performance status (PS2), who historically have been underrepresented in clinical trials.

Recent studies indicate that PS2 patients can benefit from chemotherapy, with combination treatments like carboplatin and paclitaxel potentially offering better outcomes than single-agent therapies, without significantly increased toxicity compared to fitter patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of chemotherapy in patients with poor performance status and advanced non-small cell lung cancer. Langer, C., Lilenbaum, R.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05841563

Clinical Trial of PM54 in Advanced Solid Tumors Patients. The first part of the study (phase Ia - dose escalation) will evaluate the safety and tolerability and identify the dose-limiting toxicities (DLTs) of PM54.

2. withpower.com withpower.com/trial/phase-1-neoplasms-4-2023-3f57b

PM54 for Solid Tumors This Phase 1 medical study run by PharmaMar is evaluating whether PM54 will have tolerable side effects & efficacy for patients with Solid Tumors.

3. app.trialscreen.org app.trialscreen.org/trials/phase-1-advanced-solid-tumor-clinical-pm54-advance-tumors-patients-trial-nct05841563

Clinical Trial of PM54 in Advanced Solid Tumors Patients. Participants in this study will have access to a new investigational drug (PM54) that might help shrink or stabilize their advanced solid tumors. They will also ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/401415

Clinical Trial of PM54 in Advanced Solid Tumors Patients. The first part of the study (phase Ia - dose escalation) will evaluate the safety and tolerability and identify the dose-limiting toxicities (DLTs) of PM54.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11662834/

Ecteinascidin synthetic analogues: a new class of selective ... Lurbinectedin, ecubectedin, and PM54 were effective in reducing cell proliferation and migration, as well as inducing S-phase cell cycle arrest and DNA damage.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05841563

Clinical Trial of PM54 in Advanced Solid Tumors Patients. The first part of the study (phase Ia - dose escalation) will evaluate the safety and tolerability and identify the dose-limiting toxicities (DLTs) of PM54.

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05841563/clinical-trial-of-pm54-in-advanced-solid-tumors-patients

Clinical Trial of PM54 in Advanced Solid Tumors Patients. The first part of the study (phase Ia - dose escalation) will evaluate the safety and tolerability and identify the dose-limiting toxicities (DLTs) of PM54.

8. pharmamar.com pharmamar.com/wp-content/uploads/2023/07/PharmaMar-Corporate-Presentation-Slide-Deck-July-2023.pdf

World leader in the development and commercialization of ... Solid tumors (basket trial). Monotherapy. Soft tissue sarcoma2 ... Efficacy and safety profile of lurbinectedin in 2nd-line SCLC ...

9. ctv.veeva.com ctv.veeva.com/study/clinical-trial-of-pm54-in-advanced-solid-tumors-patients

Clinical Trial of PM54 in Advanced Solid Tumors Patients. The first part of the study (phase Ia - dose escalation) will evaluate the safety and tolerability and identify the dose-limiting toxicities (DLTs) of PM54.