Clinical trial NCT06534437: MEN1703 (SEL24) to Treat Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma (JASPIS-01)
Official title: An Open Label, Phase 2 Clinical Trial of MEN1703 as Monotherapy and in Combination With Glofitamab in Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-Hodgkin Lymphoma, B-cell
Keywords: Relapsed
Refractory
Aggressive
Lead sponsor: Ryvu Therapeutics SA
Sponsor class: INDUSTRY
Collaborators: name: Menarini Group
First posted: 2024-08-02
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of the study is to assess the safety and anti-lymphoma activity of MEN1703 (Dapolsertib hydrochloride) when given as a single-agent or combined with glofitamab to patients with relapsed/refractory (R/R) aggressive B-cell non-Hodgkin lymphoma. The study will be open to groups at the same time:

* Group 1 - patients who have not had anti-CD3xCD20 bispecific antibody therapy but who have had at least 2 prior lines of systemic treatment for aggressive B-cell non-Hodgkin lymphoma
* Group 2 - patients who have exhausted all standard treatment options including at least 2 prior lines of systemic treatment for aggressive B-cell non-Hodgkin lymphoma Group 1 patients will be treated for a maximum of 12 cycles. One cycle is 21 days. Group 2 with be treated until the disease progresses, therefore treatment duration is dependent on the number of treatment cycles a participant receives prior to progression.

Detailed description: The study consists of 3 parts, to investigate MEN1703 (Dapolsertib hydrochloride) in combination with glofitamab in patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody (group 1) or MEN1703 alone in patients who have exhausted all standard treatment options (group 2).

Part 1 (safety run-in) and Part 2 (enrichment): patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody (group 1) will receive either 150 mg or 125 mg of MEN1703 along with glofitamab. Patients who have exhausted all standard treatment options (group 2) will receive 125 mg of MEN1703 as a single-agent.

Part 3 (optional randomized comparison): Patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody therapy will be randomized to receive either MEN1703 (Dapolsertib hydrochloride) at a dose selected from part 2 in combination with glofitamab or glofitamab alone.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years old
2. Documented histological confirmation of aggressive B-cell non-Hodgkin lymphoma including DLBCL NOS and transformed indolent B-cell lymphoma
3. Relapsed or refractory disease having received at least 2 prior lines of systemic treatment and, naïve to anti-CD3xCD20 bispecific antibody treatment (group 1) or exhausted all standard, available treatment options (group 2)
4. At least 1 measurable site of disease based on computed tomography (CT) or positron emission tomography (PET)-CT scan with involvement of 2 or more clearly demarcated lesions and or nodes.
5. Availability of lymph node tissue at Screening (or archival sample) (part 2 participants only)
6. Life expectancy of ≥12 weeks.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
8. Adequate organ function at Screening
9. Adequate hematologic function

Exclusion Criteria:

1. Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening.
2. Received anti-cancer treatments, including cytotoxic chemotherapy, radiotherapy, hormonal therapy, biologic, immunotherapy, or investigational drugs within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug. Prior treatment with CAR-T cell or an anti-CD3xCD20 bispecific antibody therapy (permitted for Group 2 only), requires a wash out period of ≥4 weeks.
3. Concurrent participation in another therapeutic clinical study.
4. Ongoing clinically significant toxicity (for example, alopecia is not clinically significant) from any prior anti-cancer therapy that has not resolved to Grade 1 or less prior to the first dose of study drug.
5. Prior treatment with a PIM inhibitor.
6. Group 1 only: Any prior therapy with a bispecific antibody targeting CD3 and CD20.
7. Known risk of allergy to the study drugs, MEN1703 (group 1 and 2) or glofitamab (group 1) or their excipients
8. Contraindication to all uric acid lowering agents.
9. Major surgery within 1 month prior to first dose of study drug.
10. Hematopoietic stem cell transplant within 4 months prior to first dose of study drug.
11. Requires systemic immune-modulating therapy (regardless of dose) or has confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression.
12. Exposed to live or live attenuated vaccine(s) within 4 weeks prior to signing the informed consent form (ICF).
13. Evidence of ongoing and uncontrolled systemic bacterial, fungal, or viral infection, except for documented Grade Common Terminology Criteria for Adverse Events (CTCAE) ≤2 infections with evidence of improvement or without evidence of worsening infection.
14. Known human immunodeficiency virus (HIV) infection
15. Current active liver disease from any cause
16. Ongoing drug-induced pneumonitis.
17. Ongoing inflammatory bowel disease.
18. Active known second malignancy
19. Received an agent known to be a sensitive CYP2D6 substrate or a CYP2D6 substrate with a narrow therapeutic range, a strong or moderate CYP2D6 inhibitor, or a BCRP inhibitor within 14 days or 5 half-lives (whichever is shorter), prior to the first dose of study drug.
20. Cardiac dysfunction is defined as myocardial infarction within 6 months of study entry, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled dysrhythmias, or poorly controlled angina.
21. Receiving treatment for active, ongoing thromboembolic event. Note: Does not apply to prophylactic treatment to prevent or avoid reoccurrence of a prior resolved event. To review with Medical Monitor where further risk assessment is needed.
22. History of serious ventricular arrhythmia (e.g., VT or VF, ≥3 beats in a row), or QT interval corrected for heart rate (QTc) ≥480 ms.

    Note: QTc values up to 500 ms will be acceptable where patient's medical history e.g., bundle branch block, is known to cause mild QTc prolongation and the condition is well controlled.
23. Any disease, syndrome or condition which may significantly affect drug intake via oral route.
24. Planning to become pregnant or breastfeed during treatment and for 1 month after the last dose of study drug.
25. Any other prior or current medical condition, intercurrent illness, surgical history, physical or 12-lead electrocardiogram (ECG) findings, laboratory abnormalities, or extenuating circumstance (e.g., alcohol or drug addiction) that, in the investigator's opinion, could jeopardize patient safety or interfere with the objectives of the study.

Primary outcomes:
measure: Part 1: Incidence and severity of adverse events (AE)
timeFrame: 12 months
measure: Part 2 and Part 3: Complete response (CR) (group 1)
timeFrame: 12 months
measure: Part 2 and Part 3: Overall response rate (group 2)
timeFrame: 12 months
Secondary outcomes:
measure: Part 2 and Part 3, Incidence and severity of AE
timeFrame: 12 months
measure: Maximum Plasma Concentration (Cmax)
timeFrame: 12 months
measure: Maximum Plasma Concentration (Tmax)
timeFrame: 12 months
measure: Area Under the Concentration Time-Curve (AUC)
timeFrame: 12 months
measure: Impact of treatment on patient reported outcomes (PRO)
timeFrame: 12 months
measure: Impact of treatment on quality of life (QOL)
timeFrame: 12 months
measure: Overall survival (OS)
timeFrame: 12 months
measure: Progression-free survival (PFS)
timeFrame: 12 months
measure: Duration of Response (DoR)
timeFrame: 12 months
measure: Duration of Complete Response (DoCR)
timeFrame: 12 months
measure: Time to response
timeFrame: 12 months
measure: Time to next treatment
timeFrame: 12 months
Other outcomes:
Locations:
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
city: Limoges CEDEX 1
country: France
facility: CHU de Limoges - CHU Dupuytren
city: Lyon
country: France
facility: Hospices Civils De Lyon - Hôpital Lyon Sud
city: Montpellier
country: France
facility: CHU Montpellier - Hôpital Saint Eloi
city: Paris cedex 13
country: France
facility: APHP - Hôpital Pitié-Salpêtrière
city: Pessac
country: France
facility: CHU de Bordeaux - Hôpital Haut-Lévêque
city: Biała Podlaska
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o.o.
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej Curie, Państwowy Instytut Badawczy
city: Katowice
country: Poland
facility: Pratia Hematologia Sp. z o.o.
city: Kraków
country: Poland
facility: Pratia MCM Kraków
city: Olsztyn
country: Poland
facility: Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie
city: Toruń
country: Poland
facility: Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu
city: Warsaw
country: Poland
facility: Lux Med Onkologia Sp. z o.o.
city: Warsaw
country: Poland
facility: Wojskowy Instytut Medyczny - Państwowy Instytut Badawczy
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D Hebron
city: El Palmar, Murcia
country: Spain
facility: Hospital Clínico Uni versitario Virgen de la Arrixaca
city: Madrid
country: Spain
facility: Clinica Universidad De Navarra
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Pamplona Navarra
country: Spain
facility: Hospital Universitario De Navarra
city: Pamplona
country: Spain
facility: Clinica Universidad De Navarra
city: Salamanca
country: Spain
facility: Hospital Universitario De Salamanca
city: Seville
country: Spain
facility: Hospital Universitario Virgen De La Macarena
Study officials:
References: