EP0057 in Combination With Olaparib in Relapsed Advanced Gastric Cancer and Small Cell Lung Cancer

NCT05411679 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: EP0057-202
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 21

Brief Summary

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 unmet need: extensive stage small cell lung cancer (SCLC) and ATM-negative gastric cancer (GC). EP0057-202 is a non-comparative, multi-arm, multi-centre, open label, Phase 2 study to determine the efficacy, safety, and tolerability of EP0057 in combination with olaparib (an approved PARP inhibitor) in defined patient populations with relapsed\* GC and SCLC. \*(see Eligibility Criteria for definition of "relapse" for each tumour type/population) The treatment cohorts will open sequentially at the Sponsor's discretion and patients may be enrolled into each cohort concurrently. EP0057 is an investigational nanoparticle-drug conjugate administered intravenously. The rationale for developing EP0057 is to enable selective entry of EP0057 into tumour tissue and as a result create preferential accumulation of EP0057, and therefore of the payload Camptothecin, to translate into maximum tumour cell killing.

Conditions

Gastric Cancer; Small-cell Lung Cancer

Keywords

ATM-negative gastric cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) as measured using RECIST v1.1

  Approximately 18 months

Secondary Outcomes (10)

• Progression Free Survival (PFS) as measured using RECIST v1.1

  Approximately 18 months

• Duration of Overall Response (DoR) as measured using RECIST v1.1

  Approximately 18 months

• Disease Control Rate (DCR) as measured using RECIST v1.1

  Approximately 18 months

• Overall Survival (OS) defined as time from start of study treatment until date of death due to any cause

  Approximately 18 months

• Incidence of treatment emergent adverse events (AE's) as assessed by NCI CTCAE version 5

  Approximately 18 months

Other Outcomes (7)

• Plasma levels of total and free CPT

  Approximately 18 months

• Plasma levels of total and free CPT

  Approximately 18 months

• Plasma levels of total and free CPT

  Approximately 18 months

Study Arms (2)

Arm 1

EXPERIMENTAL

patients with ataxia-telangiectasia mutated protein (ATM)-negative relapsed, advanced GC.

Drug: EP0057; Drug: Olaparib tablets

Arm 2

EXPERIMENTAL

patients with relapsed extensive stage SCLC.

Drug: EP0057; Drug: Olaparib tablets

Interventions

EP0057 DRUG

EP0057 is an investigational nanoparticle-drug conjugate with a Camptothecin payload, that is administered intravenously

Arm 1; Arm 2

Olaparib tablets DRUG

Olaparib is a PARP inhibitor (poly \[adenosine diphosphate-ribose\] polymerase inhibitor) Other names: Lynparza

Arm 1; Arm 2

Eligibility Criteria

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

You may qualify if:

• Applicable to both arms:
• Patients aged≥ 18 years (or legal age of majority in the jurisdiction) of age at the time of informed consent
• Ability to understand and provide written informed consent prior to undergoing any study procedures
• Life expectancy of \> 3 months, as estimated by the Investigator
• Presence of at least 1 measurable lesion using CT/MRI as defined by RECIST v1.1
• Adequate haematological and organ function
• Haemoglobin ≥9.0 g/dL
• ANC ≥1.5 x 10\^9/L
• Lymphocyte count ≥0.5 x 10\^9/L
• Platelet count ≥100 x 10\^9/L
• Total bilirubin ≤1.5 institutional ULN
• Serum albumin ≥2.5 g/dL
• Aspartate transaminase (AST)and alanine transaminase (ALT) ≤2.5 x ULN, unless liver metastases are present in which case, they must be ≤5xULN
• Creatinine clearance \>50 mL/min (calculated using the Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
• Patients not receiving anti-coagulant medication must have an INR of ≤1.5 and an aPTT ≤1.5xULN

You may not qualify if:

• Applicable to both arms:
• Unresolved or unstable serious toxic side-effects of prior chemotherapy or radiotherapy, ie, Grade≥2 per CTCAE (v5.0) except fatigue, alopecia, infertility, or palliative radiotherapy within 6 weeks prior to start of study treatment
• Known cerebral metastases or CNS involvement including leptomeningeal disease. SCLC patients should not have imaging older than 2 weeks prior to start of screening to exclude brain disease. For GC patients, imaging should not be older than 12 weeks prior to start of screening to exclude brain disease. Note: Any abnormal findings on brain imaging should be discussed with the Medical Monitor as part of the screening process
• Subjects with previously treated brain metastases are eligible to participate if: a) they are stable (no evidence of progression by imaging; same imaging modality \[MRI or computed tomography (CT) scan\] must be used for each assessment) for at least 28 days prior to the first dose of study drug; b) any neurologic symptoms returned to baseline; c) they have no evidence of new or enlarging brain metastases; d) they are not using corticosteroids for at least 7 days prior to the first dose of study drug.
• Malignant disease other than that being treated in this study, with the following exceptions:
• Malignancies that were treated curatively and have not recurred within 2 years prior to study treatment
• Completely resected basal cell and squamous cell skin cancers
• Any malignancy considered to be indolent and that has never required therapy
• Completely resected carcinoma in situ of any type
• Concurrent treatment with other systemic anti-cancer therapy or investigational anti-cancer drugs within 3 weeks (or 5 half-lives, whichever is longer), or 4 weeks for immunotherapy, prior to the start of study treatment
• Prior treatment with a topoisomerase I inhibitor
• History of stroke, transient ischemic attack, or myocardial infarction, within 6 months prior to C1D1
• Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (as defined as once monthly or more frequently). N. B - patients with indwelling catheters (eg, PleurX) are allowed
• Confirmed QTcF \> 470 ms on screening ECG or history of Torsades de pointes or history of congenital long QT syndrome
• Any evidence of severe or uncontrolled systemic conditions (eg, severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol

Sponsors & Collaborators

• Ellipses Pharma: lead

Study Sites (21)

Shanghai Chest Hospital

Shanghai, Changning District, 交通大学 邮政编码, 200052, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Dongan Rd, 270, Xuhui District, 200032, China

Location

Henan Cancer Hospital

Henan, Jinshui District, Zhengzhou, 450003, China

Location

Linyi Cancer Hospital

Linyi, Linyi, Lanshan District, Shandong, 276001, China

Location

The First Affiliated Hospital of Xiamen University

Fujian, Siming District, Xiamen, 361026, China

Location

Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South

Changsha, Tongzipo Road, Yuelu District, 410013, China

Location

Shanxi Cancer Hospital

Shanxi, Xinghualing District, Taiyuan, 030013, China

Location

Affiliated Hospital of Hebei University

Baoding, Yuhua East Road 212, Lianchi District, China

Location

Seoul St. Mary Hospital

Seoul, Banpo-daero 222, Banpo-dong, Seocho-gu, South Korea

Location

Dong-A University Hospital

Busan, Daesingongwon-ro 26, Seo-gu, South Korea

Location

Seoul National University Bundang Hospital

Seoul, Gumi-ro 82 173(baekchilsipsam)beo, Bundang-gu, Seongnam-si, South Korea

Location

Samsung Medical Center

Seoul, Irwon-ro 81, Gangnam-gu, South Korea

Location

South Korea University Hospital

Seoul, Jongno-gu, Daehak-ro, 101, 03080, South Korea

Location

Asan Medical Center

Seoul, Olympic-ro 88 43-gil, Songpa-gu, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, Sunhuanro 776 (1), Heungduk-gu, Cheongju-city, South Korea

Location

Cha University Bundang Medical Center

Gyeonggi-do, Yatap-ro 59, Bundang-gu, Seongnam, South Korea

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, No. 100號, Ziyou 1st Rd, Sanmin District, 80756, Taiwan

Location

Changhua Christian Hospital

Changhua, No. 176, Zhonghua Rd, 500, Taiwan

Location

Tapei Medical University - Shuang-Ho Hospital Ministry of Health and Welfare

New Taipei City, No. 291, Zhongzheng Rd, Zhonghe District, 235, Taiwan

Location

Chang Gung Medical Foundation Linkou

Taoyuan District, No.5, Fuxing St., Guishan Dist, Taiwan

Location

Chi Mei Hospital Liouying

Tainan, Yongkang District, Zhonghua Rd, 710, Taiwan

Location

MeSH Terms

Conditions

Stomach Neoplasms; Small Cell Lung Carcinoma

Interventions

olaparib

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2022
• First Posted: June 9, 2022
• Study Start: April 1, 2023
• Primary Completion: August 1, 2024
• Study Completion: December 1, 2024
• Last Updated: June 12, 2023

Record last verified: 2023-06

Locations

TW (5); CN (8); KR (8)