A study to examine the safety, tolerablity, body distribution and efficacy of [90Y]Y-PentixaTher therapy in CNS lymphoma patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pentixapharm AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Nov 2023 → ongoing

Decision date (initial)

2024-04-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Pentixapharm AG (previously PentixaPharm GmbH)

External identifiers

EU CT number

2024-512097-98-00

EudraCT number

2021-002364-43

ClinicalTrials.gov

NCT06132737

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Dose response

1. To assess the safety and tolerability of different doses of endoradiotherapy (ERT) with [90Y]Y-PentixaTher [90Y-PTT] administered once in patients with C-X-C chemokine receptor 4 (CXCR4)-positive primary or isolated secondary central nervous system (CNS) lymphoma.
2. To determine a recommended phase 2 dose.

Secondary objectives 3

1. To determine biodistribution after the administration of 90Y-PTT.
2. To determine the radiation dosimetry of 90Y-PTT (organ exposure to radiation) after administration of 90Y-PTT.
3. To undertake a preliminary assessment of the therapeutic efficacy of 90Y-PTT ERT through determination of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Conditions and MedDRA coding

Central nervous system (CNS) lymphoma; recurrent or refractory primary or isolated secondary

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Signed informed consent, by the patient or an authorized legal guardian in case the patient is temporarily not competent due to his or her disease, obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
2. Patients of either gender aged > 18 years.
3. Body weight ≤ 180 kg.
4. At least one measurable lymphoma manifestation in the CNS, either contrast-enhanced lesion in the brain parenchyma or measurable meningeal lesion.
5. Histologically, cytologically, radiologically or by detection of ctDNA mutation (MYD88/L265P) in cerebrospinal fluid confirmed relapsed/refractory PCNSL or relapsed/refractory SCNSL. Initial histologic confirmation at first diagnosis is mandatory. No peripheral lymphoma evidence is allowed.
6. Recurrent or refractory CNSL a) For recurrent disease, comprising new lesions or recurrent CNSL after a CR at that site, there are no maximum number of recurrences. b) Refractory CNSL comprises patients with non-responding CNSL to frontline therapy, or progressive disease after an initial,partial response (PR).
7. Stored stem cells with at least ≥ 2 x 10^6 CD34+ cells/kg of body weight.
8. If sexually active female patient of childbearing potential: patient agrees to take adequate contraceptive measures during study participation and agrees to continue use of this method for the duration of the study and for six months after the last dose.
9. Female patient without childbearing potential: documented history (e.g., tubal ligation or hysterectomy) or is post-menopausal.
10. For male patient whose partner is of child-bearing potential: patient is willing to ensure that he and his partner use effective contraception during the study and for six months after 90Y-PTT treatment.
11. ECOG performance status ≤ 2.
12. Confirmed presence of CXCR4 on technically evaluable tumor lesions documented by a visually CXCR4-positive [68Ga]Ga-PentixaFor PET scan within two months prior to enrolment in the study or during Screening.
13. Blood test results as follows: a. Absolute neutrophil count: > 1.0 x 10^9 /L b. Hemoglobin: ≥ 8 g/dL c. Platelets: ≥ 75 x 10^9/L d. Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP): ≤ 3 x ULN (upper limit of normal) e. Serum creatinine: ≤ 2 x ULN and Cockroft Gault calculated glomerular filtration rate (GFR) ≥ 50 mL/min f. Bilirubin: ≤ 3 x ULN.

Exclusion criteria 11

1. Known or suspected hypersensitivity to study product(s) or related products.
2. Presence of active infection, or history of serious infection six weeks prior to IMP administration. Patients with uncontrolled human immunodeficiency virus (HIV) infection as well as acute or chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded (Note: Patients on antiretroviral therapy (ART) with controlled HIV infection (defined as sufficient ART compliance, non-measurable HIV and CD4+ T helper cells > 200/microL) may be enrolled, if considered eligible for study treatment by the investigator.).
3. SCNSL with systemic involvement.
4. Brain radiation therapy ≤ 180 days before IMP infusion.
5. Any mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study, and/or evidence of an uncooperative attitude without designated legal representative.
6. Contraindication for contrast-enhanced MRI as set out in the relevant institutional guidelines (e.g., pacemaker, defibrillator, aneurysm clip, metal in the body, renal insufficiency, severe claustrophobia etc.) or contraindication for the use of gadolinium contrast for MRI.
7. Previous treatment with the IMP.
8. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice). A pregnancy test will be performed at the start of the study for all female patients of childbearing potential (i.e., not surgically sterile or two years postmenopausal).
9. Male of reproductive age who or whose partner(s) is not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).
10. Participation in any other clinical study of an approved or non-approved IMP within the last 30 days (or ≤ 5 terminal elimination half-lives of previous IMP, whichever is longer) before screening.
11. Any disorder (e.g., unstable angina pectoris, cardiac arrhythmia (excluding atrial fibrillation and atrial flutter, uncontrolled congestive heart failure), poorly controlled hypertension, poorly controlled diabetes mellitus [HbA1c ≥ 9%], etc.) or laboratory findings, except for conditions associated with CNS lymphoma, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Incidence, severity and relationship of (S)AEs (graded in severity according to NCI CTCAE version 5.0)
2. Incidence and severity of DLT
3. Changes from baseline in vital signs.
4. Changes from baseline in laboratory parameters (hematology and biochemistry, urinalysis).
5. Abnormal findings in physical examination
6. Findings 12-lead ECG
7. SCT after treatment
8. Mortality rate at 30 and 90 days post-treatment

Secondary endpoints 3

1. Biodistribution: • Maximal uptake (%) for tumor lesion • Maximal uptake (%) in discernible organs • TAC in discernible thoracic and abdominal organs, target lesion and blood • AUC of 90Y-PTT in discernible thoracic and abdominal organs, target lesion and blood • AUC of 90Y-PTT in urine
2. Radiation dosimetry: • Organ receiving the highest absorbed dose • Specific absorbed dose per organ and for target lesion • Cumulative absorbed organ/lesion doses
3. Efficacy • ORR at one month and three months • PFS at one month and three months • Rate of CR and PR at one month and three months • PFS at 12 month • OS at one month, 3 months, 12 months

Investigational products

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

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pentixapharm AG

Sponsor organisation

Pentixapharm AG

Address

Bismarckstrasse 13, Altstadt Altstadt

City

Wuerzburg

Postcode

97080

Country

Germany

Scientific contact point

Organisation

Pentixapharm AG

Contact name

Clinical trial team

Public contact point

Organisation

Pentixapharm AG

Contact name

Clinical trial team

Third parties 1

Locations

1 EU/EEA country · 2 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 11 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