Durvalumab(MEDI4736) and AZD6738 Combination Therapy in Relapsed Small Cell Lung Cancer Subjects

NCT04361825 | Completed Phase 2

• 1 other identifier: 2020-02-103
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a single arm, multi-center phase II study of durvalumab and AZD6738 combination therapy in subjects with relapsed small cell lung cancer (SCLC) as a second or third line chemotherapy.

Conditions

Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy of durvalumab and AZD6738 combination therapy in subjects with relapsed SCLC subjects as 2nd or 3rd line therapy: Objective response rate(ORR)

  Objective response rate(ORR) by RECIST 1.1

  Up to 30 months

Secondary Outcomes (4)

• Duration of response

  Up to 30 months

• Disease control rate

  8 weaks

• Overall survival(OS)

  Up to 30 months

• progression-free survival(PFS)

  Up to 30 months

Study Arms (1)

Durvalumab(MEDI4736) and AZD6738 combination

EXPERIMENTAL

Drug: Durvalumab

Interventions

Durvalumab DRUG

Durvalumab 1500mg via IV administered for every 4weeks(fixed dosing for subjects \> 30 kg body weight) in Day 1 of each cycle and AZD 6738 240mg bid per os administered in each cycle days 1 and 7. One cycle is consisted of 28 days.

Also known as: AZD6738

Durvalumab(MEDI4736) and AZD6738 combination

Eligibility Criteria

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

You may qualify if:

• Provision of fully informed consent prior to any study specific procedures.
• Subjects must be ≥ 18years of age.
• Body weight \> 30kg
• Small cell lung cancer that has progressed during or after first-line therapy.
• The 1st line regimen must have contained platinum based regimen and must have documented radiological and/or clinical progression on treatment. The subjects must not exposed to the prior immunotherapy which could have been received separately, in combination, or in sequence with platinum-doublet chemotherapy.
• Refractory to first-line chemotherapy or relapse within 6months since the last dose of first-line chemotherapy
• If the subject correspond to sensitive relapse(relapse more than 6months since the last dose of first-line chemotherapy), (s)he should get second-line treatment prior to study entry.
• Subjects are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
• ECOG performance status 0-1
• Subjects must have a life expectancy ≥ 3months from proposed first dose date.
• Subjects must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin ≥ 9.0g/dL
• White blood cells(WBC) ≥ 3 x 109/L
• Platelet count ≥ 100 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

You may not qualify if:

• Previous enrolment in the present study.
• More than two prior chemotherapy regimen for the treatment of small cell lung cancer(However, immunotherapy is not counted the prior chemotherapy regimen.)
• Subjects with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \> 2years.
• Treatment with any investigational product during the last 14days before the enrollment (or a longer period depending on the defined characteristics of the agents used).
• Subjects receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The subject can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 4weeks prior to treatment.
• Rceiving, or having received, concomitant medications, herbal supplements and/or foods that significantly modulate cytochrome P450 3A4(CYP3A4) or P-glycoprotein(P-gp) activity(washout periods of 2weeks, but 3weeks for St. John's Wort). Note these include common azole antifungals, macrolide antibiotics and other medications.
• Prior exposure to an ATR inhibitor.
• Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection, with clinically significant sequelae that would preclude adequate absorption of AZD6738
• Current or prior use of immunosuppressive medication within 14days before the first dose of durvalumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections(eg, intra-articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions(eg, CT scan premedication)
• Receipt of live attenuated vaccine within 30days prior to the first dose of investigational product. Note: Subjects, if enrolled, should not receive live vaccine whilst receiving investigational product and up to 180days after the last dose of investigational product.
• Subjects with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Subjects with irreversible toxicity not reasonably expected tobe exacerabated by treatment with durvalumab may be included only after consultation with with the Study Physician.

Sponsors & Collaborators

• Se-Hoon Lee: lead
• AstraZeneca: collaborator

Study Sites (2)

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

durvalumab; ceralasertib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Se-Hoon Lee, M.D,Ph.D.

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 12, 2020
• First Posted: April 24, 2020
• Study Start: June 17, 2020
• Primary Completion: October 25, 2023
• Study Completion: October 25, 2023
• Last Updated: January 3, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)