Durvalumab after definitive chemoradiotherapy in limited stage small cell lung cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca Farmaceutica Spain S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Jul 2025 → ongoing

Decision date (initial)

2025-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca Farmacéutica Spain S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others

To describe the safety profile of durvalumab for patients with LS-SCLC who have not progressed following CRT

Secondary objectives 5

1. To describe effectiveness of durvalumab for patients with LS-SCLC who have not progressed following CRT
2. To further describe safety profile of durvalumab for patients with LS-SCLC who have not progressed following CRT.
3. To assess factors associated with outcomes among patients treated with durvalumab with LS-SCLC who have not progressed following CRT.
4. To assess disease-related symptoms and health-related quality of life (HRQoL) in patients treated with durvalumab with LS-SCLC who have not progressed following CRT.
5. To describe immune and biological characteristics of patients at baseline, during treatment and at the end of treatment/progression.

Conditions and MedDRA coding

small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Female or male patients aged ≥18 years at the time of signing the Informed Consent Form (ICF).
2. 2. Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures. Additionally, signed and dated written genetic and/or biomarker informed consents, respectively, to collect baseline tissue and blood samples for future translational biomarker assessment at baseline, at the initiation of durvalumab maintenance treatment (cycles 1, 2, 3, 4, 7, 10, 13, 19, 26), and at end of treatment/progression.
3. 3. Patients must have histologically or cytologically documented limited stage SCLC (stage I-III SCLC [T any, N any, M0] according to the AJCC Cancer Staging Manual, [8th Edition] or the IASLC Staging Manual in Thoracic Oncology [2016]), i.e., patients whose disease can be encompassed within a radical radiation portal. Patients who are stage I or II must be medically inoperable as determined by investigator.
4. 4. WHO/ECOG PS of 0, 1 or 2 at enrolment, after CRT. A maximum of 20% of patients with ECOG 2 is allowed.
5. 5. Received an appropriate first-line concurrent or sequential chemoradiotherapy regimen as defined below, unless after consultation with the study medical team an alternative is acceptable: o Received 3-4 cycles of platinum-based chemotherapy concurrent or sequential with radiotherapy, which must be completed within 1 to 90 days prior to the first dose of durvalumab. o The chemotherapy regimen must contain platinum and IV etoposide, administered as per local SoC regimens.
6. 6. Received a total dose of radiation of 60 to 66 Gy (±10%) over approximately 6 weeks for standard QD radiation schedules or 45 Gy (±10%) over approximately 3 weeks for hyperfractionated BID radiation schedules.
7. 7. Patients must have achieved CR, PR, or SD and not have progressed following definitive, platinum-based chemoradiotherapy.
8. 8. Adequate organ and marrow function (independent of transfusion, infusion, or growth factor support for at least 14 days prior to obtaining screening labs), defined as below: o Haemoglobin ≥9.0 g/dL o Absolute neutrophil count ≥1.5 x 109/L o Platelet count ≥100 x 109/L o Serum bilirubin ≤1.5 x the ULN. This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia [predominantly unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physician. o ALT and AST ≤2.5 x ULN o Measured creatinine clearance (CL) >40 mL/min or calculated CL >40 mL/min as determined by Cockcroft-Gault (using actual body weight)
9. 9. Must have a life expectancy of at least 12 weeks.
10. 10. Body weight >30 kg.

Exclusion criteria 22

1. 1. Mixed SCLC and NSCLC histology.
2. 2. Extensive-stage SCLC.
3. 3. Any history of grade ≥2 pneumonitis.
4. 4. History of allogeneic organ transplantation.
5. 5. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn’s disease], diverticulitis [except for diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis], Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc. The following are exceptions to this criterion: o Patients with vitiligo or alopecia. o Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. o Any chronic skin condition that does not require systemic therapy. o Patients without active disease in the last 5 years may be included but only after consultation with the study physician. o Patients with celiac disease controlled by diet alone.
6. 6. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
7. 7. History of another primary malignancy except for: o Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of durvalumab and of low potential risk for recurrence. o Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. o Adequately treated carcinoma in situ without evidence of disease.
8. 8. History of leptomeningeal carcinomatosis.
9. 9. History of active primary immunodeficiency.
10. 10. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBsAg result), hepatitis C (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies).
11. 11. Any unresolved toxicity NCI Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 from previous CRT except for alopecia, vitiligo, and the laboratory values defined in the inclusion criteria: o Patients with grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician. o Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study physician.
12. 12. Brain metastases or spinal cord compression. All patients will have an MRI (preferred) or CT, preferably with IV contrast of the brain, prior to study entry, after CRT.
13. 13. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
14. 14. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
15. 15. Patients whose conditions have progressed while on CRT.
16. 16. Major surgical procedure (as defined by the Investigator) within 42 days prior to the first dose of IP.
17. 17. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: o Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection). o Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. o Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
18. 18. Participation in another clinical study with an investigational product administered in the last 4 weeks.
19. 19. Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
20. 20. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
21. 21. Female patients who are pregnant or breastfeeding and male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 3 months after the last dose of durvalumab.
22. 22. Judgment by the investigator that the patient should not participate in the study because the patient is unlikely to comply with study procedures, restrictions, and requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. • Incidence of grade ≥ 3 AEs
2. • Incidence of imAE, defined as an AE that is associated with drug exposure and is consistent with an immune-mediated mechanism of action and there is no clear alternate etiology.
3. • Incidence of AEs that lead to treatment delays/interruptions or permanent discontinuation.

Secondary endpoints 7

1. • Progression-Free Survival (PFS). Progression-Free Survival defined as the time from the date of first dose of durvalumab until the date of objective disease progression according RECIST 1.1 criteria assessed by investigator, or death (by any cause in the absence of progression). The measure of interest is the median PFS.
2. • Overall Survival (OS) rate at 36 months, defined as the percentage of patients that are still alive at 36 months.
3. • All AEs.
4. • Serious AEs.
5. • Factors to be analysed: - Gender - Age range (<65 vs ≥65 years) - Smoking status - WHO/ECOG - PD-L1 status - Disease stage - Carboplatin vs cisplatin - Type of radiotherapy: standard vs hyperfractionated - cCRT vs sCRT - Response to CRT - Time to durvalumab initiation from last CRT dose - PCI
6. Scores on the EORTC (European Organisation for Research and Treatment of Cancer) Core Quality of Life Questionnaire (EORTC QLQ-C30) and its specific module for lung cancer QLQ-LC29. Change from baseline in EORTC QLQ-C30 and EORTC QLQ-LC29 and time to deterioration in EORTC QLQ-C30.
7. Biomarker analysis of tumour tissue sample at baseline to assess exploratory markers, which may include but is not limited to PD-L expressions. Biomarker analysis of blood samples at baseline, during treatment and at the end of treatment/progression, which may include but are not limited to ctDNA.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca Farmaceutica Spain S.A.

Sponsor organisation

Astrazeneca Farmaceutica Spain S.A.

Address

Calle Del Puerto De Somport 21-23, Poligono Industrial Carretera De Burgos Poligono Industrial Carretera De Burgos

City

Madrid

Postcode

28050

Country

Spain

Scientific contact point

Organisation

Astrazeneca Farmaceutica Spain S.A.

Contact name

José Luis Lechuga

Public contact point

Organisation

Astrazeneca Farmaceutica Spain S.A.

Contact name

AstraZeneca Clinical Study Information Center

Third parties 2

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications