Olaparib and durvalumab (MEDI4736) in patients with metastatic pancreatic cancer and DNA Damage Repair genes alterations

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Asociacion Grupo Tratamiento De Tumores Digestivos

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Nov 2022 → ongoing

Decision date (initial)

2024-10-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Astra Zeneca

External identifiers

EU CT number

2024-510970-26-00

EudraCT number

2020-004859-32

ClinicalTrials.gov

NCT05659914

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of olaparib in combination with durvalumab by assessment of overall response rate (ORR).

Secondary objectives 5

1. To evaluate the efficacy of olaparib in combination with durvalumab by assessment of progression-free survival (PFS)
2. To evaluate the efficacy of olaparib in combination with durvalumab by assessment of overall survival (OS)
3. To evaluate the efficacy of olaparib in combination with durvalumab by assessment of duration of response (DoR)
4. To evaluate the efficacy of olaparib in combination with durvalumab by assessment of disease control rate (DCR)
5. To evaluate safety and tolerability of the combination of olaparib and durvalumab across subjects included in this trial.

Conditions and MedDRA coding

Metastatic pancreatic cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. 1. Males and females ≥18 years of age (at the time consent is obtained).
2. Written informed consent provided.
3. Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale (Appendix A).
4. Subject must have archival tumour tissue available for central laboratory testing of alterations in DDR genes or willing to undergo a fresh tumour biopsy.
5. Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas.
6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
7. Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas with alterations in DNA damage repair genes.
8. Presence of alterations in DDR genes in tumour tissue or blood (somatic) or blood and saliva (germinal) sample previously determined by a local assay at any time prior to Screening or by the central laboratory.
9. Patients must have received a minimum of 1 line of chemotherapy for metastatic disease and a maximum of 2 lines. Patients who have received adjuvant treatment and have recurrence within 6 months of completion of the adjuvant or neoadjuvant treatment, is counted as first line chemotherapy.
10. Patients must have received platinum-based chemotherapy and must have benefit of it and not progressed while on platinum. Benefit is defined as partial or complete response or PFS  6 months.
11. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment
12. Body weight >30 kg
13. ECOG performance status 0-1 within 14 days before enrolment (Appendix A).
14. Measurable disease as defined by RECIST version 1.1 guidelines.
15. Patients must have a life expectancy ≥ 16 weeks.
16. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 7 days of study treatment.
17. 13. Male patients must use a condom during treatment and for 3 months after the last dose of study drug when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception (see 5.3.1) if they are of childbearing potential. Male patients should not donate sperm throughout the period of taking study drug and for 3 months following the last dose of study drug.
18. Resolution of all toxic effects of prior treatments, except alopecia, to Grade 0 or 1, by NCI CTCAE version 5.0.
19. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures

Exclusion criteria 24

1. Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS).
2. Uncontrolled, clinically significant, symptomatic cardiovascular disease within 6 months before enrolment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication.
3. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
4. Persistent toxicities (≥Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
5. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
6. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
7. Patients considered a poor medical condition due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
8. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
9. Patients with an active infection.
10. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
11. Patients with known active hepatitis (i.e., Hepatitis B or C).
12. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
13. Any pre-existing medical condition of sufficient severity to prevent full compliance with the study.
14. Have received previously treatment with PARP inhibitors or PDL-1 inhibitors (including durvalumab).
15. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment.
16. Concomitant chemotherapy, hormonal therapy, immunotherapy, or any other form of cancer treatment.
17. Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
18. Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
19. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. Significant traumatic injury within 4 weeks of the first dose of study intervention.
20. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
21. Concurrent treatment or treatment within 4 weeks of study entry with any other investigational agent.
22. Patients with a known hypersensitivity to olaparib, durvalumab or any of the excipients of the product.
23. 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.
24. Female patients who are lactating and breastfeeding or have a positive pregnancy test during the Screening Period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Response Rate (ORR) defined as the percentage of patients with an investigator-assessed complete (CR) or partial response (PR) according to Response Evaluation Criteria in Solid tumours (RECIST) v1.1.

Secondary endpoints 5

1. PFS defined as the time from initial date of study treatment to the date of objective disease progression according to RECIST 1.1 criteria or death (due to any cause), whichever occurs first.
2. OS defined as the time from the initial date of the study treatment to the date of death (due to any cause), with patients alive or lost to follow-up at the analysis data cut-off date censored at their last contact date.
3. DoR defined as time from first objective response to disease progression per RECIST 1.1 criteria or death (due to any cause). For patients with response who have not progressed or died at last observation, duration of response will be censored at their last evaluable disease assessment date.
4. DCR defined as the percentage of patients who achieve complete response, partial response or stable disease.
5. Assessment of AEs graded by NCI CTCAE v5.0, vital signs and evaluation of laboratory parameters.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Asociacion Grupo Tratamiento De Tumores Digestivos

Sponsor organisation

Asociacion Grupo Tratamiento De Tumores Digestivos

Address

Calle Tellez 30 Planta 1 Oficina 4

City

Madrid

Postcode

28007

Country

Spain

Scientific contact point

Organisation

Asociacion Grupo Tratamiento De Tumores Digestivos

Contact name

Project Manager

Public contact point

Organisation

Asociacion Grupo Tratamiento De Tumores Digestivos

Contact name

Project Manager

Third parties 3

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 9 files

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

Application history

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