Trial of EP0057, a Nanoparticle Camptothecin With Olaparib in People With Relapsed/Refractory Small Cell Lung Cancer

NCT02769962 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 16010716-C-0107
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Background: EP0057 (formerly CRLX101) 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 deoxyribonucleic acid (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.
• Computed tomography (CT) scan
• Injection of EP0057 (twice per cycle)
• Olaparib prescription 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.

Conditions

Urothelial Carcinoma; Urothelial Cancer; Lung Neoplasms; Small Cell Lung Cancer; Prostate Cancer

Keywords

PARP Inhibitor; Topoisomerase I (Top1); Camptothecins; Nanoparticle Drug Conjugate; Solid Tumors

Outcome Measures

Primary Outcomes (6)

• Phase I: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of EP0057 (CLRX101) in Participants With Refractory Cancers.

  MTD/RP2D is the dose level at which no more than 1 of up to 6 participants experience dose-limiting toxicity (DLT) during the DLT evaluation period, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. DLTs will be defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (Version 4). The following toxicities, occurring during cycle 1 of the study combination, will be considered DLTs if deemed drug-related: Grade 4 neutropenia complicated by fever ≥38.5C and/or documented infection; Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia that does not resolve within 7 days or grade 3-4 thrombocytopenia complicated with hemorrhage. Grade 4 anemia that does not resolve within 7 days despite optimal therapy; and inability to begin subsequent treatment course within 28 days of the scheduled date, due to study drug toxicity.

  First 28 days

• Phase I: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Olaparib in Participants With Refractory Cancers.

  MTD/RP2D is the dose level at which no more than 1 of up to 6 participants experience dose-limiting toxicity (DLT) during the DLT evaluation period, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. DLTs will be defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (Version 4). The following toxicities, occurring during cycle 1 of the study combination, will be considered DLTs if deemed drug-related: Grade 4 neutropenia complicated by fever ≥38.5C and/or documented infection; Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia that does not resolve within 7 days or grade 3-4 thrombocytopenia complicated with hemorrhage. Grade 4 anemia that does not resolve within 7 days despite optimal therapy; and inability to begin subsequent treatment course within 28 days of the scheduled date, due to study drug toxicity.

  First 28 days

• Number of Dose Limiting Toxicities (DLTs) During the First Cycle

  DLTs will be defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (Version 4). The following toxicities, occurring during cycle 1 of the study combination, will be considered DLTs if deemed drug-related: Grade 4 neutropenia complicated by fever ≥38.5C and/or documented infection; Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia that does not resolve within 7 days or grade 3-4 thrombocytopenia complicated with hemorrhage. Grade 4 anemia that does not resolve within 7 days despite optimal therapy; and inability to begin subsequent treatment course within 28 days of the scheduled date, due to study drug toxicity, and any Grade 3-4 non-hematologic toxicity except fatigue/asthenia \<2 weeks in duration).

  First 28 days

• Expansion: Progression Free Survival (PFS) Rate in the Combination of Olaparib Plus EP0057 (CLRX101) at 16 Weeks in Small Cell Lung Cancer (SCLC) Participants

  Determine if slightly more than 50% of participants may be identified as being without progression by 16 weeks. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

  16 weeks

• Expansion: Overall Response Rate (Complete Response (CR) + Partial Response (PR) of EP0057 (CLRX101) Plus Olaparib in Participants With Urothelial Carcinoma

  Overall response rate is the best response recorded from the start of the treatment until disease progression/recurrence. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

  8 weeks

• Expansion: Overall Response Rate (Complete Response (CR) + Partial Response (PR) of EP0057 (CLRX101) Plus Olaparib in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

  Determine if slightly more than 50% of participants may be identified as being without progression by 12 weeks. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

  12 weeks

Secondary Outcomes (11)

• Occurrences of Toxicities Including Toxicity Type and Severity (Grades 1, 2, and 3) With Probable Association to Study Regimen in Participants on Expansion Cohorts

  Start of treatment through 30 days post last dose, an average of 8.26 months.

• Progression-free Survival (PFS) on Expansion Cohorts

  Every 3 months post-treatment, up until date of death from any cause or an average of 9.57 months.

• Progression-free Survival (PFS) of the Combination

  Duration of time from start of treatment to time of progression or death, whichever occurs first, up to 2.5 years

• Overall Survival (OS) of the Combination

  Date of on-study to the date of death from any cause or last follow up, up to 2.5 years

• Prostate-specific Antigen (PSA) on Metastatic Castration-Resistant Prostate Cancer (mCRPC) Expansion Cohort Reported at Time of Documented Partial Response (PR) With an 80% Confidence Interval

  40.71 weeks from start of treatment to best response date

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 6.08 months.

Study Arms (2)

1/Phase I - EP0057 (formerly CRLX101) + Olaparib

EXPERIMENTAL

EP0057 + olaparib

Drug: EP0057; Drug: olaparib; Diagnostic Test: CT scan; Diagnostic Test: CT chest, abdomen, and pelvis; Diagnostic Test: Bone scan; Diagnostic Test: ECG; Diagnostic Test: Echocardiogram; Procedure: Biopsy

2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)

EXPERIMENTAL

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

Drug: EP0057; Drug: olaparib; Diagnostic Test: CT scan; Diagnostic Test: CT chest, abdomen, and pelvis; Diagnostic Test: Bone scan; Diagnostic Test: ECG; Diagnostic Test: Echocardiogram; Procedure: Biopsy

Interventions

EP0057 DRUG

EP0057 (formerly CRLX101) intravenous (IV) every (Q) 2weeks Day 1 and Day 15, administered in 28-day cycles, until disease progression or development of intolerable side effects. Plus olaparib (by mouth (PO) days 3-13\* and days 17-26\*) administered in 28-day cycles, until disease progression or development of intolerable side effects. Phase (P)1: Dose Escalation P2: recommended phase 2 dose (RP2D). (\* On days 13 and 26, only one dose of olaparib will be administered in the morning)

Also known as: CRLX101

1/Phase I - EP0057 (formerly CRLX101) + Olaparib; 2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)

olaparib DRUG

Olaparib (by mouth (PO) days 3-13\* and days 17-26\* administered in 28-day cycles, until disease progression or development of intolerable side effects Plus EP0057 (formerly CRLX101) (intravenous (IV) every (Q) 2 weeks, Day 1 and Day 15) administered in 28-day cycles, until disease progression or development of intolerable side effects. Phase (P)1: Dose Escalation P2: recommended phase 2 dose (RP2D). (\* On days 13 and 26, only one dose of olaparib will be administered in the morning).

Also known as: Lynparza

1/Phase I - EP0057 (formerly CRLX101) + Olaparib; 2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)

CT scan DIAGNOSTIC_TEST

Screening and baseline.

Also known as: Computed tomography scan

1/Phase I - EP0057 (formerly CRLX101) + Olaparib; 2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)

CT chest, abdomen, and pelvis DIAGNOSTIC_TEST

Metastatic castration-resistant prostate cancer (mCRPC) participants only at screening, baseline, cycle 2 Day 1, and end of treatment/disease progression.

1/Phase I - EP0057 (formerly CRLX101) + Olaparib; 2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)

Bone scan DIAGNOSTIC_TEST

Metastatic castration-resistant prostate cancer (mCRPC) participants only at screening, baseline, cycle 2 Day 1, and end of treatment/disease progression.

Also known as: Bone scintigraphy

1/Phase I - EP0057 (formerly CRLX101) + Olaparib; 2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)

ECG DIAGNOSTIC_TEST

Screening, baseline, Day 1, Day 15 and cycle 2, Day 1.

Also known as: Electrocardiogram

1/Phase I - EP0057 (formerly CRLX101) + Olaparib; 2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)

Echocardiogram DIAGNOSTIC_TEST

At screening.

Also known as: Echo

1/Phase I - EP0057 (formerly CRLX101) + Olaparib; 2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)

Biopsy PROCEDURE

Baseline Day 4 and end of treatment/disease progression.

1/Phase I - EP0057 (formerly CRLX101) + Olaparib; 2/Phase II - EP0057 + Olaparib at Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eastern cooperative Oncology Group (ECOG) performance status \<=2
• Patients with treated brain metastases (surgery, whole or stereotactic brain radiation) 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 with brain metastases should not require use of enzyme-inducing antiepileptic drugs (e.g., carbamazepine, phenytoin, or phenobarbital) within 14 days before first dose and during study. Use of newer antiepileptics that do not produce enzyme induction drug-drug interactions (DDIs) is allowed.
• Patients must have normal organ and marrow function as defined below:
• leukocytes \>=3,000/mcL
• absolute neutrophil count \>=1,500/mcL without growth factor support
• platelets \>=100,000/mcL without growth factor support
• hemoglobin \>=9 g/dL, and no blood transfusion within 4 weeks.
• Hemoglobin \>10 g/dL, and no blood transfusion within 2 weeks.
• total bilirubin \<=1.5 x upper limit of normal (ULN) (unless Gilbert's Disease)
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT)\<=2.5 X institutional upper limit of normal (\<= 5X ULN if liver mets)
• creatinine \<= ULN

You may not qualify if:

• Patients who are receiving any other investigational agents.
• Persistent toxicities (\>= Common Terminology Criteria for Adverse Events (CTCAE) grade 2) with the exception of alopecia and neuropathy, caused by previous cancer therapy
• Patients who have had prior treatment with olaparib or other camptothecin inhibitors (Ulcerative Colitis (UC) expansion Cohort Only).
• Patients with myelodysplastic syndrome/acute myeloid leukemia or active pneumonitis; or baseline features suggestive of myelodysplastic syndrome or acute myelogenous leukemia on peripheral blood smear or bone marrow biopsy, if clinically indicated.
• Hypersensitivity to study therapies ...

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Schmidt KT, Huitema ADR, Dorlo TPC, Peer CJ, Cordes LM, Sciuto L, Wroblewski S, Pommier Y, Madan RA, Thomas A, Figg WD. Population pharmacokinetic analysis of nanoparticle-bound and free camptothecin after administration of NLG207 in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2020 Oct;86(4):475-486. doi: 10.1007/s00280-020-04134-9. Epub 2020 Sep 8.

  PMID: 32897402 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Lung Neoplasms; Small Cell Lung Carcinoma; Prostatic Neoplasms

Interventions

IT-101; olaparib; Tomography, X-Ray Computed; Electrocardiography; Echocardiography; Caves; Biopsy

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Electrodiagnosis; Cardiac Imaging Techniques; Ultrasonography; Geological Phenomena; Physical Phenomena; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Environment and Public Health; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Anish Thomas
• Organization: National Cancer Institute

anish.thomas@nih.gov

240-760-7343

Study Officials

• Anish Thomas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: May 12, 2016
• Study Start: May 9, 2016
• Primary Completion: April 19, 2023
• Study Completion: March 4, 2025
• Last Updated: July 28, 2025
• Results First Posted: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)