PLX038 for Ovarian Cancer

Overseen by Andrea E. Wahner Hendrickson, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Mayo Clinic

Must not be taking: UGT1A1 inhibitors

Disqualifiers: Pregnancy, Heart disease, HIV, Hepatitis, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests PLX038, a drug that stops cancer cell growth, in patients with advanced ovarian, primary peritoneal, and fallopian tube cancers. The drug aims to shrink tumors by blocking enzymes needed for cancer cells to multiply.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require treatment with UGT1A1 inhibitors during the trial.

What data supports the effectiveness of the drug PLX038 for ovarian cancer?

Research shows that SN-38, the active component in PLX038, is significantly more potent than its parent drug, irinotecan, and has been effectively used in various forms to treat cancer. Studies have demonstrated that SN-38, when linked to other molecules, can effectively target and kill cancer cells, including ovarian cancer cells, with improved solubility and delivery. ^{1 2 3 4 5}

How is the drug PLX038 different from other ovarian cancer treatments?

PLX038 is unique because it is a pegylated (coated with a protective layer) form of SN-38, which allows for better delivery and longer circulation in the body compared to standard treatments. This pegylation can potentially reduce side effects and improve the effectiveness of the drug in treating ovarian cancer. ^{6 7 8 9 10}

Research Team

Andrea E. Wahner Hendrickson, M.D.

Principal Investigator

Mayo Clinic in Rochester

Scott H. Kaufmann, M.D., Ph.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for adults with high-grade serous ovarian, primary peritoneal, or fallopian tube cancer that's spread and resistant to platinum-based therapy. Participants need measurable disease, a life expectancy of at least 12 weeks, decent physical function (ECOG PS 0-2), acceptable blood counts and organ function. They must not have had more than one prior treatment for resistant disease and be willing to undergo biopsies.

Inclusion Criteria

Provide written informed consent

You are expected to live for at least 12 more weeks.

Women who could become pregnant must have a negative pregnancy test within 7 days before joining the study.

Exclusion Criteria

I have not had immunotherapy in the last 4 weeks.

Persons of childbearing potential who are unwilling to employ adequate contraception

I have not had radiotherapy in the last 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive PLX038 intravenously over 1 hour on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Up to 18 weeks (6 cycles)

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and every 6 months for up to 5 years.

5 years

1 visit at 30 days, then every 6 months

Treatment Details

Interventions

• Pegylated SN-38 Conjugate PLX038 (Topoisomerase I inhibitor)

Trial Overview The trial is testing PLX038, a pegylated SN-38 conjugate designed to shrink tumors in metastatic cancers by blocking enzymes needed for cell growth. It includes CT scans and biospecimen collection like blood draws and tumor biopsies to study the drug's effects.

Participant Groups

Group I: Treatment (pegylated SN-38 conjugate PLX038) Experimental Treatment 4 Interventions

Patients receive PLX038 IV over 1 hour on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, biopsy, as well as blood and stool sample collection during screening and on the trial.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

The study developed three antibody-drug conjugates (T-SN38 A, B, and C) that link the potent drug SN-38 to the anti-HER2 antibody trastuzumab, showing 2 to 3 times greater cytotoxicity against ovarian cancer cells compared to SN-38 alone.

In vivo tests revealed that all T-SN38 conjugates had significantly higher anti-ovarian cancer effectiveness than trastuzumab, with T-SN38 B demonstrating the best potency, indicating strong potential for treating HER2-positive ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis, characterization and targeting chemotherapy for ovarian cancer of trastuzumab-SN-38 conjugates. Yao, Y., Yu, L., Su, X., et al.[2018]

The new PEG-SN38 conjugate significantly improves the water solubility of SN38, increasing it by 400- to 1000-fold, which allows for better administration and potential effectiveness in treating cancer.

In preclinical tests, PEG-SN38 demonstrated anticancer activity comparable to native SN38 and superior efficacy compared to CPT-11 in a mouse model, making it a promising candidate for further development in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel prodrugs of SN38 using multiarm poly(ethylene glycol) linkers. Zhao, H., Rubio, B., Sapra, P., et al.[2022]

SN-38, a highly potent metabolite of irinotecan, has been successfully formulated into nanoparticles using a folate-conjugated polymer, enhancing its solubility and stability for potential clinical use.

These folate-targeted nanoparticles demonstrated significantly greater cytotoxicity against HT-29 cancer cells compared to non-targeted nanoparticles, suggesting they could be an effective delivery system for SN-38 in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT-29 cell lines. Ebrahimnejad, P., Dinarvand, R., Sajadi, A., et al.[2022]

Labetuzumab govitecan (IMMU-130) significantly enhances the delivery of the active drug SN-38 to human colonic tumor xenografts, achieving up to 300-fold more SN-38 in tumors compared to irinotecan, while also minimizing exposure in normal tissues.

In preclinical studies with mice, IMMU-130 maintained higher serum levels of SN-38 over time and demonstrated a gradual release of the drug, indicating a more effective and potentially safer treatment option for targeting CEA-producing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective and Concentrated Accretion of SN-38 with a CEACAM5-Targeting Antibody-Drug Conjugate (ADC), Labetuzumab Govitecan (IMMU-130). Sharkey, RM., Govindan, SV., Cardillo, TM., et al.[2020]

The bioconjugate ONCOFID-S, which links the drug SN-38 to hyaluronan, effectively targets ovarian cancer cells via the CD44 receptor, showing comparable tumor growth inhibition to free SN-38 in vitro.

In a mouse model, ONCOFID-S demonstrated improved therapeutic efficacy and better tolerability than the standard drug CPT-11, without causing inflammation, suggesting it could be a promising strategy for treating ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug conjugation to hyaluronan widens therapeutic indications for ovarian cancer. Montagner, IM., Merlo, A., Carpanese, D., et al.[2020]

Pegylated liposomal doxorubicin (PLD) has been an effective treatment for platinum-sensitive recurrent ovarian cancer, with clinical trials showing overall mean survival times of up to 29 months.

Combining PLD with carboplatin has shown similar effectiveness to other platinum-based therapies but with a better safety profile, and ongoing trials are exploring combinations with other innovative therapies to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of pegylated liposomal doxorubicin in the management of platinum-sensitive recurrent ovarian cancer: current concepts. Rakowski, JA., Ahmad, S., Holloway, RW.[2018]

In a clinical trial involving 115 patients with ovarian, fallopian tube, and peritoneal cancer, PLD demonstrated a confirmed overall response rate (ORR) of 37.4%, indicating its efficacy in treating patients who experienced cancer progression after platinum-based therapy.

PLD was associated with a low frequency of severe adverse events, with only 3% of patients experiencing grade 3 or higher side effects, suggesting it is a safe treatment option that maintains a high quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer. Yuan, Z., Zhang, Y., Cao, D., et al.[2023]

CT-2103, a new drug combining paclitaxel and poly-L-glutamic acid, showed a 10% response rate in heavily pretreated patients with recurrent ovarian cancer, indicating some efficacy, especially in those with fewer prior treatments.

The treatment was associated with a notable incidence of neuropathy (30% of patients), which was higher than expected, suggesting the need for careful monitoring of side effects in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of CT-2103 in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Sabbatini, P., Aghajanian, C., Dizon, D., et al.[2017]

In a study of 30 patients with advanced ovarian cancer who had a complete response to initial chemotherapy, pegylated liposomal doxorubicin (PLD) was found to be a feasible consolidation therapy, with 79% of patients completing all four treatment cycles.

The treatment showed promising outcomes, with a median overall survival of 31 months and 47% of patients remaining disease-free at 4 years, although palmar-plantar erythrodysesthesia was the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin consolidation therapy after platinum/paclitaxel-based chemotherapy for suboptimally debulked, advanced-stage epithelial ovarian cancer patients. Rocconi, RP., Straughn, JM., Leath, CA., et al.[2018]

The combination of trabectedin and pegylated liposomal doxorubicin (PLD) is effective for treating patients with partially platinum-sensitive recurrent ovarian cancer, especially those who have had multiple prior platinum-based treatments.

A case study of a 64-year-old woman showed that this combination therapy led to a sustained clinical response and good tolerance over more than two years, highlighting its potential as a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance with Trabectedin in the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer. Guerra Alía, EM., Sempere Ortega, C., Cortés Salgado, A., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Synthesis, characterization and targeting chemotherapy for ovarian cancer of trastuzumab-SN-38 conjugates. [2018]

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

Novel prodrugs of SN38 using multiarm poly(ethylene glycol) linkers. [2022]

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

Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT-29 cell lines. [2022]

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

Selective and Concentrated Accretion of SN-38 with a CEACAM5-Targeting Antibody-Drug Conjugate (ADC), Labetuzumab Govitecan (IMMU-130). [2020]

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

Drug conjugation to hyaluronan widens therapeutic indications for ovarian cancer. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Use of pegylated liposomal doxorubicin in the management of platinum-sensitive recurrent ovarian cancer: current concepts. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer. [2023]

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

Phase II study of CT-2103 in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin consolidation therapy after platinum/paclitaxel-based chemotherapy for suboptimally debulked, advanced-stage epithelial ovarian cancer patients. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Maintenance with Trabectedin in the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer. [2022]