Maintenance Durvalumab (MEDI4736) and Olaparib (AZD2281) After Standard 1st Line Treatment (Carboplatin/Cisplatin, Etoposide, Durvalumab) in HRD Positive Extensive Disease (ED) Small-cell Lung Cancer (SCLC) (GUIDANCE)

A Multicenter Phase II Trial of Maintenance Durvalumab (MEDI4736) and Olaparib (AZD2281) After Standard 1st Line Treatment (Carboplatin/Cisplatin, Etoposide, Durvalumab) in Homologous Recombination Deficiency (HRD) Positive Extensive Disease (ED) Small-cell Lung Cancer (SCLC)

Maintenance durvalumab (MEDI4736) and olaparib (AZD2281) after standard 1st line treatment (carboplatin/ cisplatin, etoposide, durvalumab) in HRD positive extensive disease (ED) small-cell lung cancer (SCLC)

Study Overview

• Status: Not yet recruiting
• Conditions: Small Cell Lung Carcinoma
• Intervention / Treatment: Drug: Durvalumab; Drug: Olaparib

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jürgen Wolf, MD; Phone Number: 89050 +49 221 478; Email: juergen.wolf@uk-koeln.de
• Study Contact Backup: Name: Felix John, MD; Email: felix.john@uk-koeln.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria Pre-Screening:

• Newly diagnosed, histologically documented advanced or metastatic small-cell lung cancer (UICC stage III which is not amenable to curative radiochemotherapy or stage IV). [...]
• Either de novo biopsies collected as part of routine clinical practice or archival tumor samples (taken ≤6 months prior to screening) are acceptable.
• Planned or ongoing treatment with carboplatin/cisplatin, etoposide, durvalumab as 1st-line SoC. Pre-screening must begin no later than the start of the 3rd cycle to allow sufficient time for molecular analyses. [...]
• Available radiographic chest and abdominal CT or MRI scans performed up to 42 days before initial first line treatment with carboplatin/cisplatin, etoposide and durvalumab.
• At least one measurable site of disease as defined by RECIST v1.1 criteria.
• [...]

Inclusion Criteria Screening:

• Completed pre-screening with fulfillment of all inclusion and exclusion criteria of pre-screening. Pre-screening must have tested positive for homologous recombination deficiency as defined in this protocol at central testing. [...]
• Patients must not have radiographic or clinic disease progression while on induction therapy and/or prior to start of study treatment.
• Patients must have received 4 cycles (21-day cycles) of chemoimmunotherapy with carboplatin or cisplatin, etoposide and durvalumab completed within 1 to 14 days prior to initiation of study treatment on C5D1.
• Adequate organ and marrow function

Exclusion Criteria Pre-Screening:

• Induction therapy other than carboplatin/cisplatin, etoposide and durvalumab.
• Radiographic or clinical evidence of progressive disease.
• Negative HRD result in a previous pre-screening in this trial.
• [...]

Exclusion Criteria Screening:

• Patients with symptomatic uncontrolled central nervous system (CNS) metastases.
• Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• History of leptomeningeal carcinomatosis.

• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy. Exceptions are:

  1. Alopecia (any Grade)
  2. Vitiligo (any Grade)
  3. Hypothyroidism stable on hormone replacement (Grade ≤2)
  4. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician
  5. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or olaparib may be included only after consultation with the Sponsor.
  6. ...

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination of olaparib and durvalumab after four cycles of standard 1st line treatment; Study treatment (olaparib and durvalumab) starts with the initiation of maintenance therapy and is administered at a 28-day cycle until progression, unacceptable toxicity, or discontinuation for other reasons. Induction therapy (four cycles of carboplatin/cisplatin, etoposide, durvalumab) is administered as part of standard of care.

Drug: Durvalumab; 1500 mg i.v. Q4W; Other Names: MEDI4736; IMFINZI; Drug: Olaparib; 300 mg BID orally; Other Names: AZD2281; LYNPARZA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS according to investigator-assessed RECIST 1.1 from start of maintenance therapy	Approximately two years (from First patient in (FSI) to Last patient last visit (LSLV))

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity and grading of adverse events (AE) and seriouse adverse events (SAE).	Grading is based on CTCAE Version 5	Approximately two years (from FSI to LSLV)
ORR of maintenance.	Grading is based on RECIST 1.1	Approximately two years (from FSI to LSLV)

Collaborators and Investigators

• Sponsor: University of Cologne
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 3, 2024
• First Submitted That Met QC Criteria: May 16, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib; Durvalumab
• Other Study ID Numbers: Uni-Koeln-5159; 2024-512373-27-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes