EF-39 PANOVA-4: Study of Tumor Treating Fields Concomitant With Atezolizumab, Gemcitabine and Nab-Paclitaxel as First-Line Treatment for Metastatic Pancreatic Ductal Adenocarcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novocure GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

16 Aug 2023 → 16 Jan 2026

Decision date (initial)

2024-10-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Novocure GmbH Switzerland

External identifiers

EU CT number

2024-515407-19-00

EudraCT number

2022-003157-55

WHO UTN

U1111-1309-1539

ClinicalTrials.gov

NCT06390059

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the disease control rate (DCR) by RECIST v1.1 in patients with 1L mPDAC treated with TTFields concomitant with atezolizumab, gemcitabine and nab-paclitaxel.

Secondary objectives 7

1. 1. To evaluate the overall survival (OS) in patients with 1L mPDAC treated with TTFields concomitant with atezolizumab, gemcitabine and nab-paclitaxel.
2. 2. To evaluate the progression free survival (PFS) by RECIST v1.1 in patients with 1L mPDAC treated with TTFields concomitant with atezolizumab, gemcitabine and nab-paclitaxel.
3. 3. To evaluate the 1-year survival rate in patients with 1L mPDAC treated with TTFields concomitant with atezolizumab, gemcitabine and nab-paclitaxel.
4. 4. To evaluate the objective response rate (ORR) by RECIST v1.1 in patients with 1L mPDAC treated with TTFields concomitant with atezolizumab, gemcitabine and nab-paclitaxel.
5. 5. To evaluate the PFS rate at 6 months (PFS6) in patients with 1L mPDAC treated with TTFields concomitant with atezolizumab, gemcitabine and nab-paclitaxel.
6. 6. To evaluate the duration of response (DOR) by RECIST v1.1 in patients with 1L mPDAC treated with TTFields concomitant with atezolizumab, gemcitabine and nab-paclitaxel.
7. 7. To evaluate the safety and tolerability profile of TTFields concomitant with atezolizumab, gemcitabine and nab-paclitaxel in patients with 1L mPDAC.

Conditions and MedDRA coding

Metastatic pancreatic ductal adenocarcinoma (mPDAC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1. Signed Informed Consent Form for the study protocol.
2. 2. 18 years of age and older at the time of signing Informed Consent Form.
3. 3. ECOG performance status of 0-1.
4. 4. Histologically or cytologically confirmed de-novo diagnosis of metastatic pancreatic ductal adenocarcinoma.
5. 5. No prior treatment for PDAC.
6. 6. Life expectancy equal to or greater than 3 months.
7. 7. Measurable disease in the abdomen, as defined by RECIST v1.1.
8. 8. Preferably, tumor accessible for tissue collection. Consent to provide blood and tumor tissue for exploratory study is highly encouraged. Patients who cannot or are unwilling to provide tissue or blood for the exploratory study are not excluded from the study. • If tumor tissue is available, a formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or approximately 10-15 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study treatment initiation. • If FFPE specimens described above are not available, any type of specimens (including fine-needle aspiration, cell pellet specimens [e.g., from pleural effusion], and lavage samples) are also acceptable. This specimen should be accompanied by the associated pathology report. • As mentioned above, if tumor tissue is not available (e.g., depleted because of prior diagnostic testing), patients are still eligible.
9. 9. Amenable and assigned by the investigator to receive therapy with gemcitabine and nab- paclitaxel.
10. 10. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: a. ANC ≥ 1.5 X 109/L (1500/μL) without granulocyte colony-stimulating factor support within 14 days prior to initiation of study treatment. b. Lymphocyte count ≥ 0.5 X 109/L (500/μL). c. WBC count ≥2.5x109/L (2500/ μL). d. Platelet count ≥ 100 X 109/L (100,000/μL) without transfusion. e. Hemoglobin ≥ 90 g/L (9 g/dL). Patients may be transfused to meet this criterion. f. AST, ALT, and ALP ≤ 2.5 X upper limit of normal (ULN), with the following exceptions: Patients with documented liver metastases: AST and/or ALT ≤ 5 X ULN. Patients with documented liver or bone metastases: ALP ≤ 5 X ULN. g. Total bilirubin ≤ 1.5 X ULN with the following exception: Patients with known Gilbert disease: total bilirubin ≤ 3 X ULN. h. Creatinine ≤ 1.5 X ULN. i. Albumin ≥ 25 g/L (2.5 g/dL). j. For patients not receiving therapeutic anticoagulation: INR/PT or aPTT/PTT ≤ 1.5 X ULN.
11. 11. For patients receiving therapeutic anticoagulation: stable anticoagulation regimen.
12. 12. Negative hepatitis B surface antigen (HBsAg) test at screening
13. 13. Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: • Negative total hepatitis B core antibody (HBcAb) • Positive total HBcAb test followed by a negative (per local laboratory definition) hepatitis B virus (HBV) DNA test The HBV DNA test must be performed for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test.
14. 14. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test must be performed for patients who have a positive HCV antibody test.
15. NOTE: A full list of inclusion criteria is available in the section 4.1 (pages 27-29) of the study protocol.

Exclusion criteria 7

1. 1. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. Asymptomatic patients with treated CNS lesions are eligible, provided that all of the following criteria are met: • The patient has no history of intracranial hemorrhage or spinal cord hemorrhage. • The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment. • The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. • Anticonvulsant therapy at a stable dose is permitted.
2. 2. History of leptomeningeal disease.
3. 3. Uncontrolled tumor-related pain • Patients requiring pain medication must be on a stable regimen at study entry. • Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to treatment initiation. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Palliative radiotherapy is permitted, provided it does not interfere with the assessment of tumor target lesions (e.g., the lesion to be irradiated must not be the only site of measurable disease). • Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy, if appropriate, prior to treatment initiation.
4. 4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage procedure (i.e., more than one time per month). • Patients with indwelling catheters (e.g. PleurX®) are allowed
5. 5. Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected calcium >ULN)
6. 6. Active or history of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome or multiple sclerosis, with the following exceptions: • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible for this study • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible for this study • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: o Rash must cover <10% of body surface area o Disease is well controlled at baseline and only requiring low-potency topical steroids o No acute exacerbations of underlying condition within the last 12 months requiring treatment with either psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral steroids
7. NOTE: A full list of exclusion criteria is available in the section 4.2 (pages 29-31) of the study protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease control rate (DCR) by RECIST v1.1 in patients with 1L mPDAC treated with TTFields concomitant with atezolizumab, gemcitabine and nab-paclitaxel, measured as the proportion of patients with stable disease for at least 16 weeks or confirmed PR or CR.

Secondary endpoints 2

1. 1. Overall survival (OS) in patients with 1L mPDAC treated with TTFields concomitant with atezolizumab, gemcitabine and nab-paclitaxel, measured as the period between the time of treatment initiation and the time of death.
2. NOTE: A full list of secondary endpoints is available in the section 3.2.2 (page 26) of the study protocol.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novocure GmbH

Sponsor organisation

Novocure GmbH

Address

Neuhofstrasse 21

City

Baar

Postcode

6340

Country

Switzerland

Scientific contact point

Organisation

Novocure GmbH

Contact name

Novocure Scientific contact point

Public contact point

Organisation

Novocure GmbH

Contact name

Novocure Public contact point

Third parties 3

Locations

3 EU/EEA countries · 13 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 19 files

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

Application history

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