A Phase 3 Study Comparing Pirtobrutinib to Ibrutinib in CLL/SLL

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Loxo Oncology Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Aug 2022 → ongoing

Decision date (initial)

2024-05-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Loxo Oncology, Inc.

External identifiers

EU CT number

2023-507699-38-00

EudraCT number

2021-003206-41

WHO UTN

U1111-1300-5677

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

Part 1:
To evaluate overall response rate (ORR) of pirtobrutinib (Arm A) compared to ibrutinib (Arm B)

Part 2:
To evaluate ORR of pirtobrutinib in patients with del(17p) who are treatment naïve

Conditions and MedDRA coding

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
3. Adequate organ function • Platelets greater than or equal to (≥)50 x 10⁹/liter (L) or ≥30 x 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis, • Hemoglobin ≥8 grams/deciliter (g/dL) or ≥6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis • Absolute neutrophil count ≥0.75 x 10⁹/L or ≥0.50 × 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis • Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min).
4. Part 1 - Known 17p deletion status (wildtype or deleted). Part 2 – Must have deletion of 17p as determined by FISH testing performed in a CLIA, ISO/IEC, CAP, or other similarly certified laboratory as per local guidelines, including, but not limited to, IVDR compliance as applicable.

Exclusion criteria 18

1. Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment.
2. Known or suspected central nervous system (CNS) involvement.
3. A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease.
4. Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]).
5. Significant cardiovascular disease including ejection fraction < 40% and any grade ongoing atrial fibrillation or atrial flutter.
6. Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests.
7. Active cytomegalovirus (CMV) infection.
8. Active uncontrolled systemic bacterial, viral, or fungal infection.
9. Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count.
10. Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments.
11. Ongoing inflammatory bowel disease.
12. Part 1: Prior exposure to BTK inhibitor (covalent or noncovalent). Part 2: Prior therapy for CLL
13. Concurrent use of investigational agent or anticancer therapy except hormonal therapy.
14. Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
15. Use of > 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug.
16. Vaccination with a live vaccine within 28 days prior to randomization.
17. Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment.
18. Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Part 1 and Part 2: Primary endpoint: Overall response rate (ORR) as assessed by independent review committee (IRC) per iwCLL 2018 criteria. ORR is defined as the proportion of patients who achieve a BOR of CR, CRi, nPR, or PR at or before the initiation of subsequent anticancer therapy.

Investigational products

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

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Loxo Oncology Inc.

Sponsor organisation

Loxo Oncology Inc.

Address

281 Tresser Boulevard Floor 9th

City

Stamford

Postcode

06901-3238

Country

United States

Scientific contact point

Organisation

Loxo Oncology Inc.

Contact name

Lilly Clinical Trials information desk

Public contact point

Organisation

Loxo Oncology Inc.

Contact name

Lilly Clinical Trials information desk

Third parties 10

Locations

9 EU/EEA countries · 55 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 112 files

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

Application history

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