Beschreibung

INCMOR 0208-301 - Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tafasitamab Plus Lenalidomide in Addition to Rituximab Versus Lenalidomide in Addition to Rituximab in Patients With Relapsed/Refractory (R/R) Follicular Lymphoma Grade 1 to 3a or R/R Marginal Zone Lymphoma

Studientherapie

Treatment Group A:
· Tafasitamab 12 mg/kg IV on Days 1, 8, 15, and 22 of Cycles 1 to 3 and on Days 1 and 15 (every second week) of Cycles 4 to 12. Cycle length 28 days.
Plus
· Rituximab (including biosimilars) 375 mg/m2 IV every week in Cycle 1 on Days 1, 8, 15, and 22 and on Day 1 of every 28-day cycle from Cycle 2 to 5.
Plus
· Lenalidomide (including generics) 20 mg PO once daily on Days 1 to 21 of every 28-day cycle for 12 cycles.
Treatment Group B:
· Tafasitamab placebo (0.9% saline solution) IV on Days 1, 8, 15, and 22 of Cycles 1 to 3 and on Days 1 and 15 (every second week) of Cycles 4 to 12. Cycle length 28 days.
Plus
· Rituximab (including biosimilars) 375 mg/m2 IV every week in Cycle 1 on Days 1, 8, 15, and 22 and on Day 1 of every 28-day cycle from Cycles 2 to 5.
Plus
· Lenalidomide (including generics) 20 mg PO once daily on Days 1 to 21 of every 28-day cycle for 12 cycles.

Studienstatus

Rekrutierung gestartet/nimmt Patienten auf

Allgemeine Infos zum Antrag

Frau Dr. Katrin Edmaier-Schröger
kedmaierschroeger@incyte.com

Incyte Biosciences Germany GmbH (Unternehmen, 11881)
Fraunhoferstr. 9
81152 Planegg (Martinsried)

To compare the efficacy of tafasitamab and lenalidomide in addition to rituximab to the efficacy of placebo and lenalidomide in addition to rituximab in terms of PFS in participants with R/R FL.

To compare the efficacy of tafasitamab and lenalidomide in addition to rituximab versus placebo and lenalidomide in addition to rituximab in terms of PFS in the overall population (FL and MZL).
To compare the efficacy of tafasitamab and lenalidomide in addition to rituximab versus placebo and lenalidomide in addition to rituximab in terms of PET-CR rate at EOT, MRD-negativity rate at EOT, and OS in the FL population.

Male and female participants at least 18 years of age who have a histologically confirmed Grade 1, 2 or 3a FL or histologically confirmed nodal MZL, splenic MZL, or extranodal MZL of the MALT.
· Must have been previously treated with at least 1 prior systemic anti-CD20 immunotherapy or chemo-immunotherapy. This includes treatments such as rituximab monotherapy or chemotherapy plus immunotherapy with rituximab or obinutuzumab, with or without maintenance.
· Must have documented relapsed, refractory, or PD after treatment with systemic therapy:
- Relapsed lymphoma: relapsed after initial response of CR to prior therapy.
- Refractory lymphoma: achieved less than PR to the last treatment or achieved a CR or PR that lasted less than 6 months before lymphoma progression.
- Progressive lymphoma: PD after initial response of PR or SD to prior therapy.

total number of 174 PFS events in the FL population are required to detect a HR of 0.65 with 80% power for the primary analysis, using a 2-sided log-rank test at an alpha level of 5% and a 1:1 randomization ratio between the 2 treatment groups. A total of 528 participants with R/R FL need to be randomized 1:1 with stratification (264 participants per treatment group), assuming a median PFS of 27.8 months for lenalidomide in addition to rituximab, 21 months of enrollment, 12 months of follow-up for PFS and 15% of dropouts.
A minimum of 60 and up to 90 additional participants with R/R MZL will be randomized at a 1:1 ratio to 1 of the 2 treatment groups. The number of participants with MZL is based on an expected enrollment proportion of FL and MZL participants.
Approximately 275 centers globally (Europe, Asia Pacific [APAC], North America) will be participating in this study.

PFS by investigator (INV) assessment in the FL population, using Lugano 2014 criteria (Cheson et al 2014). PFS is defined as the time from randomization to first documented disease progression, or death from any cause, whichever occurs first.

PFS by INV assessment in the overall population (FL and MZL populations).
PET-CR rate at EOT (4-8 weeks after last treatment) by INV in the FL population.
· MRD-negativity rate (< 1 residual tumor cell per 104 normal cells [in peripheral blood and BM]) at EOT in the FL population.
· OS in the FL population.

Spezifische Infos zum Antrag

Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
1. Age e 18 years.
2. Ability to comprehend and willingness to sign a written ICF for the study.
3. Histologically confirmed Grade 1, 2, or 3a FL or histologically confirmed nodal MZL, splenic MZL, or extranodal MZL of the MALT as assessed locally (Swerdlow et al 2016).
Note: Participants with gastric MZL and evidence of Helicobacter pylori must have a documented nonresponse to antibiotic therapy.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
1. Age e 18 years.
2. Ability to comprehend and willingness to sign a written ICF for the study.
3. Histologically confirmed Grade 1, 2, or 3a FL or histologically confirmed nodal MZL, splenic MZL, or extranodal MZL of the MALT as assessed locally (Swerdlow et al 2016).
Note: Participants with gastric MZL and evidence of Helicobacter pylori must have a documented nonresponse to antibiotic therapy.
f. In the opinion of the investigator, be able to understand and comply with all study-related procedures, medication use, and evaluations.
g. In the opinion of the investigator, not have a history of noncompliance or be considered potentially unreliable and/or uncooperative.
6. Tumor tissue sufficient for retrospective central pathology review and correlative studies must be provided as an adjunct to participation in this study. If an archival specimen is not available, a fresh biopsy is required prior to randomization (refer to the Laboratory Manual). Note: a fresh biopsy must be considered if the relapse is within 24 months from the initial diagnosis to exclude transformed cases and potentially misdiagnosed cases.
7. Must have been previously treated with at least 1 prior systemic anti-CD20 immunotherapy or chemo-immunotherapy. This includes treatments such as the following: rituximab monotherapy or chemotherapy plus immunotherapy with rituximab or obinutuzumab, with or without maintenance. Note: At least 6 doses of anti-CD20 immunotherapy must have been given in prior therapy. Note: Systemic therapy does not include, for example, local involved field radiotherapy for limited stage disease, HBV/HCV therapy, or H pylori eradication.
8. Must have documented relapsed, refractory, or PD after treatment with systemic therapy.
a. Relapsed lymphoma: relapsed after initial response of CR to prior therapy.
b. Refractory lymphoma: achieved less than PR to the last treatment or achieved a CR or PR that lasted less than 6 months before lymphoma progression.
c. Progressive lymphoma: PD after initial response of PR or SD to prior therapy.
9. Must be in need of treatment for relapsed, refractory, or PD as assessed by the investigator according to GELF criteria (see Appendix G).
a. Participants must have at least 1 measurable disease site. A radiographically measurable lymphadenopathy is defined as at least 1 nodal lesion > 1.5 cm in longest diameter or at least 1 extranodal lesion > 1.0 cm in longest diameter (Cheson et al 2014). The lesion must be confirmed to be PET-positive at the latest at the time of randomization.
10. ECOG performance status of 0 to 2.
11. Participants with laboratory values at screening defined in Table 6.

Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1. Women who are pregnant or breastfeeding.
2. Any histology other than FL and MZL or clinical evidence of transformed lymphoma by INV assessment.
3. History of radiation therapy to e 25% of the BM for other diseases.
4. History of prior nonhematologic malignancy except for the following:
a. Malignancy treated with curative intent and with no evidence of active disease for more than 2 years before screening.
b. Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer.
c. Adequately treated carcinoma in situ without current evidence of disease.
5. History of congestive heart failure requiring the use of ongoing maintenance therapy for life-threatening arrhythmias.
6. Participants with:
a. Known positive test result for HCV (with anti-HCV serology testing) and a positive test for HCV RNA.
Note: Participants with positive serology must have been tested for HCV RNA and are eligible only in the case of negative HCV RNA.
b. Known positive test result for chronic HBV infection (defined by HBsAg positivity).
Note: Participants with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA was undetectable, provided that they are willing to undergo monthly ongoing DNA testing. Antiviral prophylaxis may be administered as per institutional guidelines. Participants who have protective titers of HBsAb (HBsAb positive, HBcAb negative, and HBsAg negative) after vaccination or previously cured hepatitis B are eligible.
c. Known seropositive for or history of active viral infection with human immunodeficiency virus.
7. Active systemic infection.
8. Participants in a severely immunocompromised state.
9. Known CNS lymphoma involvement.
10. Uncontrolled intercurrent illness.
11. History or evidence of clinically significant cardiovascular, CNS, and/or other systemic disease that would, in the investigator's opinion, preclude participation in the study or compromise the participant's ability to give informed consent.
12. Life expectancy < 6 months.
13. History or evidence of rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
14. Major surgery (excluding lymph node biopsy) within 28 days prior to signing the ICF unless the participant is recovered at the time of signing the ICF.
15. Any systemic antilymphoma and/or investigational therapy within 28 days prior to the start of Cycle 1.
16. Prior use of lenalidomide in combination with rituximab.
17. History of hypersensitivity to compounds of similar biological or chemical composition to tafasitamab, immunomodulatory drugs, rituximab, other monoclonal antibodies, and/or the excipients contained in the study drug formulations.
18. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.

The study duration for an individual participant is divided into the screening period (up to 28 days), treatment period (twelve 28-day cycles), EOT (4-8 weeks after last treatment), and follow-up period (60 months after EOT). The total duration is up to approximately 6 years per participant.

Approximately 275 centers globally
Approximately 15 centers in Germany

Incyte Corporation 1801 Augustine Cut-Off Wilmington, Delaware 19803
Contact: Oliver Manzke, Katrin Edmaier-Schröger

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