NCT04538378

Olaparib (LYNPARZA) Plus Durvalumab (IMFINZI) in EGFR-Mutated Adenocarcinomas That Transform to Small Cell Lung Cancer (SCLC) and Other Neuroendocrine Tumors

Terminated Phase 2 Results posted Last updated 27 January 2025

What this trial tests

Phase 2 trial testing Olaparib in EGFR-Mutated Non-Small-Cell Lung Carcinoma in 4 participants. Terminated before completion.

Timeline

7 July 2021

Primary endpoint
22 March 2023

27 February 2024

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	4
Start date	7 July 2021
Primary completion	22 March 2023
Estimated completion	27 February 2024
Sites	1 location across United States

Drugs / interventions tested

• Olaparib (olaparib) — full drug profile →
• Durvalumab — full drug profile →
• EKG
• Tumor biopsy
• CT chest, abdomen and pelvis
• MRI chest, abdomen and pelvis

Conditions studied

• EGFR-Mutated Non-Small-Cell Lung Carcinoma — all drugs for EGFR-Mutated Non-Small-Cell Lung Carcinoma →
• Small Cell/Neuroendocrine — all drugs for Small Cell/Neuroendocrine →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with EGFR-Mutated Non-Small-Cell Lung Carcinoma or Small Cell/Neuroendocrine. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Best Overall Response (BOR) Primary · Disease progression; an average of 53 days

BOR is the best response recorded from the start of the treatment until disease progression/recurrence. The clinical response rate of evaluable participants will be reported along with a 95% confidence interval according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions. Stable disease (SD) is neither sufficient shrinkage

Complete Response

Group	Value	95% CI
1/Arm 1: Combination of Durvalumab and Olaparib	0	0 – 0

Partial Response

Group	Value	95% CI
1/Arm 1: Combination of Durvalumab and Olaparib	0	0 – 0

Progressive Disease

Group	Value	95% CI
1/Arm 1: Combination of Durvalumab and Olaparib	1.0	1.0 – 1.0

Stable Disease

Group	Value	95% CI
1/Arm 1: Combination of Durvalumab and Olaparib	0	0 – 0

Progression-free Survival (PFS) Secondary · Disease progression, an average of 7 weeks

PFS is defined as the time interval from start of treatment to documented evidence of disease progression assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). PFS will be estimated by the Kaplan-Meier method. The median PFS will be reported along with a 95% confidence interval. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions.

Group	Value	95% CI
1/Arm 1: Combination of Durvalumab and Olaparib	53	35 – 55

Number of Participants With Grades 1, 2, 3, 4 and/or 5 Serious and/or Non-serious Toxicity Secondary · Treatment phase, an average of 12 weeks

Participants will be assessed for toxicity by reporting the grades of toxicity and the type of toxicity observed for all participants. Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or su

Anemia

Group	Value	95% CI
Grade 1 Non-Serious	1
Grade 2 Non-Serious	0
Grade 3 Non-Serious	0
Grade 4 Non-Serious	0
Any Grade Serious	0

Anorexia

Group	Value	95% CI
Grade 1 Non-Serious	1
Grade 2 Non-Serious	1
Grade 3 Non-Serious	0
Grade 4 Non-Serious	0
Any Grade Serious	0

Anxiety

Group	Value	95% CI
Grade 1 Non-Serious	1
Grade 2 Non-Serious	0
Grade 3 Non-Serious	0
Grade 4 Non-Serious	0
Any Grade Serious	0

Constipation

Group	Value	95% CI
Grade 1 Non-Serious	3
Grade 2 Non-Serious	0
Grade 3 Non-Serious	0
Grade 4 Non-Serious	0
Any Grade Serious	0

Cough

Group	Value	95% CI
Grade 1 Non-Serious	0
Grade 2 Non-Serious	1
Grade 3 Non-Serious	0
Grade 4 Non-Serious	0
Any Grade Serious	0

Dizziness

Group	Value	95% CI
Grade 1 Non-Serious	1
Grade 2 Non-Serious	0
Grade 3 Non-Serious	0
Grade 4 Non-Serious	0
Any Grade Serious	0

Dyspnea

Group	Value	95% CI
Grade 1 Non-Serious	0
Grade 2 Non-Serious	2
Grade 3 Non-Serious	0
Grade 4 Non-Serious	0
Any Grade Serious	0

Fatigue

Group	Value	95% CI
Grade 1 Non-Serious	1
Grade 2 Non-Serious	3
Grade 3 Non-Serious	0
Grade 4 Non-Serious	0
Any Grade Serious	0

Overall Survival (OS) Secondary · At death, an average of 275 days

OS is defined as the time between the first day of treatment to the day of death. OS will be estimated by the Kaplan-Meier method. The median OS will be reported along with a 95% confidence interval.

Group	Value	95% CI
1/Arm 1: Combination of Durvalumab and Olaparib	284	136 – 397

Number of Participants With Serious and/or Non-Serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Secondary · 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 11.4 weeks

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent

Group	Value	95% CI
1/Arm 1: Combination of Durvalumab and Olaparib	4

Adverse events — posted to ClinicalTrials.gov

Time frame: All-Cause Mortality was monitored/assessed an average of 275 days. 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 11.4 weeks.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1/Arm 1: Combination of Durvalumab and Olaparib

Serious: 0/4 (0%)

Deaths: 4/4

Other adverse events (24 terms — click to expand)

Reaction	System	1/Arm 1: Combination of Du…
Constipation	Gastrointestinal disorders	—
Fatigue	General disorders	—
Lymphocyte count decreased	Investigations	—
Nausea	Gastrointestinal disorders	—
Anorexia	Metabolism and nutrition disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Hypokalemia	Metabolism and nutrition disorders	—
Anemia	Blood and lymphatic system disorders	—
Anxiety	Psychiatric disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Dizziness	Nervous system disorders	—
Headache	Nervous system disorders	—
Hyperglycemia	Metabolism and nutrition disorders	—
Hyperkalemia	Metabolism and nutrition disorders	—
Hyponatremia	Metabolism and nutrition disorders	—
Lipase increased	Investigations	—
Pain	General disorders	—
Paresthesia	Nervous system disorders	—
Serum amylase increased	Investigations	—
Superficial thrombophlebitis	Vascular disorders	—
Thyroid stimulating hormone increased	Investigations	—
Tremor	Nervous system disorders	—
Urticaria	Skin and subcutaneous tissue disorders	—
Vomiting	Gastrointestinal disorders	—

Data from ClinicalTrials.gov NCT04538378 adverse events section.

Sponsor's own description

Background:

Lung cancers with epidermal growth factor receptor (EGFR) mutations may develop resistance to therapies targeting this protein by evolving/being transformed into small cell or neuroendocrine cancers. There are no standard treatments for it. Researchers want to see if a new combination of drugs can help.

Objective:

To see if the combination of durvalumab and olaparib will cause tumors to shrink.

Eligibility:

Adults age 18 and older who had EGFR-mutated non-small-cell lung carcinoma (NSCLC) that was treated and now transformed to SCLC or another neuroendocrine tumor.

Design:

Participants will be screened under a separate protocol. They may have a tumor biopsy.

Participants will have a physical exam. They will have a review of their symptoms, their medicines, and their ability to do their normal activities. They will have blood tests. They will have an electrocardiogram to evaluate their heart.

Participants will have a computed tomography (CT) scan, a series of x-rays taken of parts of the body.

Participants will get durvalumab on Day 1 of each 28-day cycle. It is given through a small plastic tube that is put in an arm vein. They will take olaparib by mouth twice every day. They will keep a medicine diary.

Participants will take the study drugs until their disease gets worse or they have unacceptable side effects.

About 30 days after they stop taking the study drugs, participants will have a follow-up visit. Then they will be contacted every 6 months for the rest of their life....

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options.
   Gomatou G, Syrigos N, Kotteas E. · · 2023 · cited 98× · PMID 36765799 · DOI 10.3390/cancers15030841
2. Emerging advances in defining the molecular and therapeutic landscape of small-cell lung cancer.
   Sen T, Takahashi N, Chakraborty S, Takebe N, et al · · 2024 · cited 79× · PMID 38965396 · DOI 10.1038/s41571-024-00914-x
3. The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy.
   Shi C, Qin K, Lin A, Jiang A, et al · · 2022 · cited 60× · PMID 36071479 · DOI 10.1186/s13046-022-02469-0
4. The Mechanisms of PD-L1 Regulation in Non-Small-Cell Lung Cancer (NSCLC): Which Are the Involved Players?
   Lamberti G, Sisi M, Andrini E, Palladini A, et al · · 2020 · cited 38× · PMID 33114576 · DOI 10.3390/cancers12113129
5. Acquired Resistance to Osimertinib in <i>EGFR</i>-Mutated Non-Small Cell Lung Cancer: How Do We Overcome It?
   Bertoli E, De Carlo E, Del Conte A, Stanzione B, et al · · 2022 · cited 34× · PMID 35805940 · DOI 10.3390/ijms23136936
6. New Generations of Tyrosine Kinase Inhibitors in Treating NSCLC with Oncogene Addiction: Strengths and Limitations.
   Attili I, Corvaja C, Spitaleri G, Del Signore E, et al · · 2023 · cited 32× · PMID 37894445 · DOI 10.3390/cancers15205079
7. Detecting Small Cell Transformation in Patients with Advanced EGFR Mutant Lung Adenocarcinoma through Epigenomic cfDNA Profiling.
   El Zarif T, Meador CB, Qiu X, Seo JH, et al · · 2024 · cited 25× · PMID 38912901 · DOI 10.1158/1078-0432.ccr-24-0466
8. The potential of PARP inhibitors in targeted cancer therapy and immunotherapy.
   Hunia J, Gawalski K, Szredzka A, Suskiewicz MJ, et al · · 2022 · cited 25× · PMID 36533080 · DOI 10.3389/fmolb.2022.1073797