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

45 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: EP0057 consists of a sugar molecule cyclodextrin linked to a chemotherapy drug called camptothecin. The combined molecule or "nanoparticle drug conjugate" travels through the blood. Once inside cancer cells, the chemotherapy drug is released from the molecule. Olaparib is a drug that may stop cancer cells from repairing the DNA damage caused by chemotherapy. 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 small cell lung cancer (SCLC). 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 older with small cell lung cancer. Design: Participants will be screened with standard cancer care tests. Participants will get the 2 study drugs in 28-day cycles. EP0057 will be given every 2 weeks, through a small plastic tube in an arm vein. Olaparib will be taken by mouth twice a day most days. Participants will keep a pill diary. For Cycle 1, participants will have 3 visits. All other cycles will have 2 visits. At study visits, participants may have: * Blood and hair samples taken * History and Physical exam * Questions about health and side effects * Pregnancy test * Optional tumor biopsy where a piece of tumor is removed by needle after numbing the skin. * CT scan * Injection of EP0057 (twice per cycle) * Olaparib prescription \<TAB\> Participants will have a follow-up visit 4 weeks after finish taking the drugs. They will have a physical exam and blood tests. They may have a tumor biopsy. The study team will call the patient every 3 months for follow up after completing the study treatment.

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.

What data supports the idea that EP0057 + Olaparib for Small Cell Lung Cancer is an effective drug?

The available research shows that combining Olaparib with another drug, Temozolomide, in patients with relapsed small cell lung cancer resulted in a 41.7% response rate, meaning that nearly half of the patients saw their cancer shrink or stop growing. Additionally, patients lived for a median of 8.5 months after starting the treatment, which suggests that this combination could be a promising option for those whose cancer has returned after initial treatment. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination EP0057 + Olaparib for Small Cell Lung Cancer?

Olaparib, a part of the treatment, has shown promise in treating small cell lung cancer (SCLC) when combined with other drugs, with a study showing a 41.7% response rate in relapsed SCLC patients. This suggests that Olaparib could be effective in combination therapies for SCLC. ^{1 2 3 4 5}

What safety data is available for EP0057 and Olaparib in treating small cell lung cancer?

Safety data for Olaparib (Lynparza) is available from various studies. It has been evaluated in Japanese and Chinese patients with advanced solid tumors, showing its safety and tolerability. Additionally, Olaparib has been studied in small cell lung cancer in combination with ceralasertib, focusing on its clinical efficacy. However, specific safety data for the combination of EP0057 and Olaparib in small cell lung cancer is not directly mentioned in the provided research. ^{1 3 6 7 8}

Is the combination of EP0057 and Olaparib safe for humans?

Olaparib (Lynparza) has been studied for safety in patients with advanced solid tumors, including in Japanese and Chinese populations, and is generally considered safe, though specific side effects can vary. It is important to discuss potential risks and side effects with your healthcare provider before participating in a clinical trial. ^{1 3 6 7 8}

Is the drug EP0057, Olaparib a promising treatment 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 suggest it could be beneficial for small cell lung cancer, especially when combined with other treatments. ^{1 2 4 9 10}

How is the drug EP0057 + Olaparib unique for treating small cell lung cancer?

The combination of EP0057 and Olaparib is unique for treating small cell lung cancer because it involves a novel use of Olaparib, a drug that inhibits a specific enzyme (PARP) involved in DNA repair, which is being explored for its potential to enhance the effectiveness of existing treatments and delay cancer progression in this aggressive cancer type. ^{1 2 4 9 10}

Research Team

Anish Thomas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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.

Inclusion Criteria

Criterion: You are over 18 years old and have been diagnosed with small cell lung cancer. You have already tried standard chemotherapy or immune-checkpoint inhibitor treatment and your disease has continued to progress. You have evidence of measurable disease and are in a condition where you can take oral medications. You must also meet specific organ and marrow function requirements, and agree to use contraception if capable of having children. Additionally, you must be able to understand and sign a consent form.

Phase I: Patients must have histologically or cytologically confirmed advanced solid tumor that is resistant or refractory to standard therapy. A minimum of 2 weeks will be required from any prior therapy, including chemotherapy, immunotherapy and/or radiation. In addition, recovery to Grade <= 1 from all reversible toxicities related to prior therapy is required at study entry. Patients do not need to have measurable disease to enroll on phase I. Age 18 years. ECOG performance status <=2. Patients with treated brain metastases are allowed provided the lesions have been stable for at least 2 weeks and the patient is off steroids or is on a stable dose of steroids. Patients must have normal organ and marrow function as defined. Women of child-bearing potential and men must agree to use adequate contraception. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Criterion: You have advanced prostate cancer that has spread, and have already been treated with certain medications. You must have low levels of testosterone, and be in good overall health. You must also agree to certain medical procedures and use contraception if applicable.

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

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

Treatment Details

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.

Participant Groups

Group I: 2/Phase II Experimental Treatment 2 Interventions

EP0057 + olaparib at MTD/RP2D

Group II: 1/Phase I Experimental Treatment 2 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+

Findings from Research

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]

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 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]

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 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]

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]

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]

References

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

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

2. Ireland 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. [2022]

3. United States 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. [2023]

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

Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer. [2020]

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

Safety evaluation of olaparib for treating ovarian cancer. [2015]

6. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. [2022]

7. Germany 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. [2020]

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

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

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

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

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

Olaparib: first global approval. [2020]