EP0057 + Olaparib for Small Cell Lung Cancer

Overseen By Danielle F Pinkiert, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Enzyme-inducing antiepileptics

Disqualifiers: Myelodysplastic syndrome, Acute myeloid leukemia, Active pneumonitis, others

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

Compensation: Varies

Number of Visits: 3

Duration: 28-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining two drugs, EP0057 and olaparib, to treat small cell lung cancer (SCLC). EP0057 is a chemotherapy drug that directly targets cancer cells, while olaparib (also known as Lynparza) prevents cancer cells from repairing themselves after chemotherapy damage. The trial aims to determine the best dosage and assess how well this combination works against SCLC. It is suitable for adults with SCLC who have experienced disease progression despite previous treatments like chemotherapy or immune therapy. Participants will receive the drugs in 28-day cycles and undergo regular health checks throughout the study. 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 combination therapy.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a requirement for a minimum of 2 weeks from any prior therapy, including chemotherapy, immunotherapy, and/or radiation, before starting the trial. Additionally, patients with brain metastases should not use enzyme-inducing antiepileptic drugs within 14 days before the first dose and during the study. It's best to discuss your specific medications with the study team.

Will I have to stop taking my current medications?

The trial requires a minimum of 2 weeks without any prior therapy, including chemotherapy, immunotherapy, or radiation, before starting the study drugs. Additionally, patients with brain metastases should not use certain antiepileptic drugs within 14 days before the first dose and during the study. Other medications are not specifically mentioned, so it's best to discuss with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is testing the safety of combining EP0057 and olaparib to treat small cell lung cancer. Olaparib, a drug that prevents cancer cells from repairing chemotherapy-induced damage, has been shown to be safe in other studies and is already FDA-approved for different uses, indicating a known safety profile.

EP0057 is a newer treatment that uses a sugar molecule to deliver a chemotherapy drug directly into cancer cells. Researchers are still testing this method to determine its safety and the highest safe dose. As this trial is in its early stages, the main goal is to understand how people tolerate these drugs when used together.

While specific safety results from earlier tests aren't detailed here, the treatment remains under careful review to ensure safety for further testing. Researchers closely monitor participants for any side effects during the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy treatments for small cell lung cancer, EP0057 and olaparib offer a novel approach by combining a nanoparticle-drug conjugate with a PARP inhibitor. EP0057, formerly known as CRLX101, is designed to deliver a more targeted attack on cancer cells, potentially reducing side effects often associated with traditional chemotherapy. Olaparib enhances this effect by blocking the cancer cells' ability to repair their DNA, making them more susceptible to damage. Researchers are particularly excited about this combo because it could lead to more effective treatment outcomes with potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

This trial will evaluate the combination of EP0057 and olaparib for treating small cell lung cancer (SCLC). Research has shown that this combination could be promising. Olaparib has effectively treated other cancers, such as ovarian and breast cancer, suggesting it might also benefit SCLC. EP0057 is a specialized drug that uses tiny particles to deliver chemotherapy directly to cancer cells, releasing the medicine inside them. This targeted method aims to attack cancer cells while causing less harm to healthy cells. The combination works by preventing cancer cells from repairing themselves, increasing their likelihood of destruction by the treatment. Early results are encouraging, but further research is needed to confirm its benefits specifically for SCLC. ^{1 2 4 6 7}

Who Is on the Research Team?

Anish Thomas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with small cell lung cancer that's gotten worse after treatment can join this trial. They need to have stable health, including normal organ and marrow function, and be off or on a steady dose of steroids if they've had brain metastases. Women who can get pregnant and men must use birth control.

Exclusion Criteria

You cannot be receiving any other experimental medications. If you have experienced significant side effects from previous cancer treatment, except for hair loss and nerve-related issues, you may not participate. If you have been treated with olaparib or similar drugs (for UC expansion Cohort only), you are not eligible. Additionally, if you have certain blood disorders or severe allergic reactions to the study treatments, you cannot take part.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive EP0057 and olaparib in 28-day cycles. EP0057 is administered intravenously every 2 weeks, and olaparib is taken orally twice a day on most days.

28-day cycles

Cycle 1: 3 visits, Subsequent cycles: 2 visits per cycle

Follow-up

Participants have a follow-up visit 4 weeks after finishing the treatment. They will have a physical exam and blood tests, and may have a tumor biopsy. The study team will call the patient every 3 months for follow-up after completing the study treatment.

4 weeks

1 visit (in-person), followed by calls every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• EP0057
• Olaparib

Trial Overview Researchers are testing EP0057, a new drug made from sugar and chemotherapy linked together, given through an IV every two weeks. Olaparib is another drug taken orally twice daily that may stop cancer cells from fixing DNA damage caused by chemo.

How Is the Trial Designed?

Group I: 2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D) Experimental Treatment 8 Interventions

EP0057 (formerly CRLX101) + olaparib at maximum tolerated dose/recommended phase 2 dose (MTD/RP2D)

Group II: 1/Phase I - EP0057 (formerly CRLX101) + Olaparib Experimental Treatment 8 Interventions

EP0057 + olaparib

EP0057 is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Olaparib is an oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[2020]

Olaparib is an effective treatment for patients with platinum-sensitive, relapsed BRCA-mutated high-grade serous ovarian cancer, showing significant improvement in progression-free survival compared to placebo in a study of 265 patients.

The treatment is generally well tolerated, with most side effects being mild to moderate, although fatigue, anemia, and neutropenia were noted as more severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. Frampton, JE.[2016]

The pharmacokinetic (PK) profile of olaparib in Chinese patients with advanced solid tumors is similar to that observed in Western and Japanese populations, confirming that the recommended dose of 300 mg twice daily is appropriate for this group.

When olaparib was combined with paclitaxel, there was a significant decrease in olaparib exposure, and while adverse events were rare, hematological side effects were more common in patients receiving the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of olaparib tablets as monotherapy and in combination with paclitaxel: results of a Phase I study in Chinese patients with advanced solid tumours. Yuan, P., Shentu, J., Xu, J., et al.[2020]

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

In a Phase I study involving 28 Japanese patients with advanced solid tumors, olaparib tablets at doses of 200 and 300 mg twice daily were found to be tolerable, with no dose-limiting toxicities reported.

The most common side effects included nausea, decreased appetite, anemia, and constipation, but no confirmed antitumor responses were observed, leading to the selection of 300 mg bid as the recommended dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. Yonemori, K., Tamura, K., Kodaira, M., et al.[2022]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

In a study involving 220 patients with small cell lung cancer (SCLC) who had a response to initial chemotherapy, the PARP inhibitor olaparib did not significantly improve progression-free survival (PFS) compared to placebo, with median PFS of 3.7 months for olaparib versus 2.5 months for placebo.

Common side effects of olaparib included fatigue, nausea, and anemia, and the rate of treatment discontinuation due to toxicity was similar to that seen in other studies, indicating that while olaparib is generally well-tolerated, it does not provide a clear benefit in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib as maintenance treatment in patients with chemosensitive small cell lung cancer (STOMP): A randomised, double-blind, placebo-controlled phase II trial. Woll, P., Gaunt, P., Danson, S., et al.[2022]

In a phase 2 study involving patients with relapsed or refractory small cell lung cancer (SCLC), olaparib alone showed a modest objective response rate of 6.7% and a disease control rate of 33.3%, indicating limited efficacy as a monotherapy.

The combination of olaparib with ceralasertib resulted in a slightly lower objective response rate of 3.8% but a higher disease control rate of 42.3%, suggesting that while neither treatment met efficacy endpoints, the combination may offer better disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker-driven phase 2 umbrella trial: Clinical efficacy of olaparib monotherapy and combination with ceralasertib (AZD6738) in small cell lung cancer. Park, S., Kim, YJ., Min, YJ., et al.[2023]

The combination of olaparib and temozolomide showed a promising overall response rate of 41.7% in a phase I/II trial involving 50 patients with previously treated small-cell lung cancer (SCLC), indicating its potential as an effective treatment option.

A molecular signature was identified that correlates low expression of inflammatory-response genes with resistance to the treatment, helping to predict which tumors are more likely to respond to the olaparib/temozolomide combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer. Farago, AF., Yeap, BY., Stanzione, M., et al.[2020]

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02769962

Study Details | NCT02769962 | Trial of EP0057, a ... Objectives: To test the safety and maximum dose of EP0057 and olaparib together. To test how well they treat small cell lung cancer. Eligibility: Adults ...

2. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=16-C-0107&&query=

A Phase I/II Trial of EP0057, a Nanoparticle Camptothecin ... Researchers want to see how safe it is to give EP0057 andolaparib together and to see how well the combination treats a specific type of lung cancer called ...

3. bcan.org bcan.org/clinicaltrials/trial-of-crlx101-a-nanoparticle-camptothecin-with-olaparib-in-people-with-relapsed-refractory-small-cell-lung-cancer/

Trial of CRLX101, a Nanoparticle Camptothecin With ... Researchers want to see how safe it is to give EP0057 and olaparib together and to see how well the combination treats a specific type of lung cancer called ...

4. withpower.com withpower.com/trial/phase-2-lung-neoplasms-4-2016-6a37d

EP0057 + Olaparib for Small Cell Lung Cancer Yes, Olaparib shows promise as a treatment for small cell lung cancer. It has been effective in other cancers like ovarian and breast cancer, and studies ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0753332222008472

PARP inhibitors in small cell lung cancer: The underlying ... A PARP inhibitor can target the DNA damage response pathway, prevent DNA repair, and induce homologous recombination deficiency (HRD) tumors.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-03324

Trial of EP0057, a Nanoparticle Camptothecin With ... Objectives: To test the safety and maximum dose of EP0057 and olaparib together. To test how well they treat small cell lung cancer. Eligibility: Adults 18 and ...

7. trial.medpath.com trial.medpath.com/clinical-trial/44482d73d6790ac0/safety-efficacy-ep0057-olaparib-gastric-cancer

EP0057 in Combination With Olaparib in Relapsed Advanced ... The aim of EP0057 - 202 is to assess the safety and efficacy of EP0057 in combination with Olaparib (a PARP inhibitor) in two cancers where there is a high ...