A Study to Evaluate the Safety and Pharmacokinetics of a Modified Tafasitamab IV Dosing Regimen Combined with Lenalidomide in Patients with Worsening (relapsed) or Unresponsive (refractory) Diffuse Large B-Cell Lymphoma (R/R DLBCL) (MINDway)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Corp., Incyte Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Neoplasms [C04]

Trial duration

17 Mar 2022 → ongoing

Decision date (initial)

2024-03-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Incyte Corp.

External identifiers

EU CT number

2023-507993-42-00

EudraCT number

2021-003855-40

ClinicalTrials.gov

NCT05222555

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic, Safety

• To evaluate the safety and tolerability of tafasitamab administered once every 2 weeks (Q2W)/once every 4 weeks (Q4W) in combination with lenalidomide in R/R DLBCL patients
• To determine a recommended dose for tafasitamab Q2W/Q4W administration in combination with lenalidomide in R/R DLBCL patients

Secondary objectives 1

1. • To evaluate the pharmacokinetic profile of tafasitamab after Q2W/Q4W dosing in combination with lenalidomide • To assess anti-tumor activity of tafasitamab after Q2W/Q4W dosing in combination with lenalidomide • To assess the incidence of anti-drug antibodies to tafasitamab

Conditions and MedDRA coding

Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1. Capable of giving signed informed consent as described in Appendix 2: Regulatory, Ethical, and Trial Oversight Considerations, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. Patient must be at least 18 years of age and of legal age (whichever is higher) in the jurisdiction in which the study is taking place at the time of signing the informed consent. 3. One of the following histologically confirmed diagnoses: • DLBCL not otherwise specified (NOS) • T cell/histiocyte-rich large B-cell lymphoma (THRLBCL) • Epstein-Barr virus (EBV) positive DLBCL of the elderly (EBV-positive DLBCL) • Grade 3b Follicular Lymphoma • Composite lymphoma with a DLBCL component with a subsequent DLBCL relapse, according to the Revised European American Lymphoma/World Health Organization (REAL/WHO) classification. Additionally, patients with the evidence of histological transformation to DLBCL from an earlier diagnosis of low-grade lymphoma (i.e., an indolent pathology such as follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia) into DLBCL with a subsequent DLBCL relapse are also eligible. 4. Tumor tissue for retrospective central pathology review must be provided as an adjunct to participation in this study. If archival formalin fixed paraffin embedded tumor tissue acquired ≤3 years prior to screening is not available, a fresh tumor tissue sample from the patient should be obtained. Archival formalin fixed- paraffin embedded tumor tissue acquired >3 years prior to screening is acceptable only in cases where a fresh tumor biopsy cannot be collected due to a safety risk, e.g., due to co-morbidity, or inaccessible tumor site.
2. 5. Patients must have:a. Relapsed and/or refractory disease as defined in Appendix 3: Study Specific Definitions b. At least one bi-dimensionally measurable disease site. The lesion must have a greatest transverse diameter of ≥ 1.5 cm and greatest perpendicular diameter of ≥ 1.0 cm at baseline. The lesion must be positive on positron emission tomography (PET) scan (for definition see Juweid et al., 2007)c. Received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must have included a cluster of differentiation-20 (CD20) targeted therapy (e.g., rituximab [RTX])d. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 6. Patients that are not eligible to undergo intensive salvage therapy including autologous stem cell transplantation (ASCT). The reason for a patient’s ineligibility must meet one of the criteria described below and documented in the patient’s source data:a. Inadequate performance status (Karnofsky performance status ≤ 80%; seeAppendix 5: Karnofsky Performance Status Scale) b. Disease not responsive to salvage chemotherapy. Responsiveness is defined as a tumor demonstrating either complete response (CR) or partial response (PR) to salvage chemotherapy c. Inadequate major organ function (any of the below): i. symptomatic congestive heart failure ii. lung function-forced vital capacity (FVC), forced expiratory volume in 1 second (FEV-1), and corrected diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 60% iii. liver function-total serum bilirubin and transaminases > 2 x upper limit of normal (ULN) d. History or evidence of significant co-morbid medical or psychiatric illness which would significantly compromise the patient’s clinical care and chances of survival e.Inability to collect adequate stem cell graft (e.g. < 1–2 x 106 CD34+ cells free of tumor contamination/kg recipient body weight)
3. 7. Patients must meet the following laboratory criteria at screening: a. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (unless secondary to bone marrow involvement by DLBCL as demonstrated by recent bone marrow aspiration and bone marrow biopsy) b. Platelet count ≥ 75 × 109/L (unless secondary to bone marrow involvement by DLBCL as demonstrated by recent bone marrow aspiration and bone marrow biopsy) c. Total serum bilirubin ≤ 2.5 × ULN unless secondary to Gilbert’s syndrome or documented liver involvement by lymphoma. Patients with Gilbert’s syndrome or documented liver involvement by lymphoma may be included if their total bilirubin is ≤ 5 × ULN (see exclusion criterion 6g) d. Alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) ≤ 3 × ULN or < 5 × ULN in cases of documented liver involvement e. Serum creatinine CL must be ≥ 60 mL/minute either measured or calculated using a standard Cockcroft and Gault formula (see Appendix 6: Cockcroft- Gault Formula)8. Patients who received previous CD19 targeted therapy (other than tafasitamab) must have CD19 positive lymphoma confirmed on a biopsy taken since completing the prior CD19 targeted therapy 9. Patients with primary refractory disease (Appendix 3: Study Specific Definitions) who received at least one, but no more than three previous systemic regimens (including a CD20 targeted therapy) for the treatment of DLBCL are eligible.

Exclusion criteria 3

1. 1. General provisions: a. Patients who are legally institutionalized, or patients under judicial protection b. Concurrent enrollment in another interventional clinical study 2. Patients who have: a. Any other histological type of lymphoma including primary mediastinal (thymic) large B-cell (PMBL) or Burkitt lymphoma b. Known “double/triple hit” genetics (high grade B-cell lymphoma) characterized by simultaneous detection of MYC with BCL2 and/or BCL6 translocation(s) defined by fluorescence in situ hybridization. MYC, BCL2, BCL6 testing prior to study enrollment is not required 3. Patients who have: a. Not discontinued (within 14 days prior to Day 1 dosing): CD20 targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma-specific therapy b. Undergone major surgery (within 4 weeks prior to Day 1 dosing) or suffered from significant traumatic injury c. Received live vaccines (within 4 weeks prior to Day 1 dosing) (See Appendix 7: Covid-19: Infection Prophylaxis and Vaccines) d. Required parenteral antimicrobial therapy for active, intercurrent infections (within 14 days prior to Day 1 dosing) 4. Patients who: a.Have, in the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies b. Were previously treated with tafasitamab or IMiDs® (e.g., thalidomide, LEN) c. Have a history of hypersensitivity to compounds of similar biological or chemical composition to tafasitamab, IMiDs® and/or the excipients contained in the study treatment formulations d. Have undergone ASCT within the period ≤ 3 months prior to signing the ICF. Patients who have a more distant history of ASCT must exhibit full hematological recovery before enrollment into the study e. Have undergone previous allogenic stem cell transplantation f.Have a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or are at high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolism (VTE) prophylaxis during the entire treatment period g. Concurrently use other anticancer or experimental treatments
2. 5. History of other malignancy that could affect compliance with the protocol or interpretation of results. Exceptions:a. Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for > 2 years prior to enrollment are eligible b. Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible 6. Patients with: a. Positive hepatitis B and/or C serology (see Appendix 8: Hepatitis Virus Serology for details) b. Known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV) c.Central nervous system (CNS) lymphoma involvement – present or past medical history d. 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 patient’s ability to give informed consent e. History or evidence of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption f. Gastrointestinal (GI) abnormalities (issue with absorption) including the inability to take oral medication g. History or evidence of severe hepatic impairment (total serum bilirubin > 3 mg/dL), jaundice unless secondary to Gilbert’s syndrome or documented liver involvement by lymphoma (see inclusion criterion 7c) h. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical class i. Any other medical condition which, in the investigator’s opinion, makes the patient unsuitable for the study
3. 7. Contraception provisions: Females: Due to the teratogenic potential of LEN, FCBP must follow the rules listed below (otherwise excluded): a. Not be pregnant as confirmed by a negative serum pregnancy test at screening and a medically supervised urine pregnancy test prior to starting study therapy b. Refrain from breast feeding and donating oocytes during the study and for 3 months after the last dose of study drug or according to local guidelines for LEN, whichever is longer c. Agree to ongoing pregnancy testing during the course of the study, and after study treatment has ended. This includes pregnancy testing and counseling if a patient misses her period or if there is any abnormality in her menstrual bleeding and applies even if the patient practices complete sexual abstinence d. Commit to continued abstinence from heterosexual intercourse if it is in accordance with her lifestyle (which must be reviewed on a monthly basis) or agree to use and be able to comply with the use of highly effective contraception without interruption at least 4 weeks prior to start of study drugs, during the study treatment and for 3 months after the last dose of study drug, or, for LEN, according to the local guidelines, whichever is longer. 8. Due to the teratogenic potential of lenalidomide, male participants must follow the rules listed below (otherwise excluded):a. Use an effective barrier method of contraception without interruption if the patient is sexually active with a FCBP. Male patients should refrain from donating sperm during the study participation and for 3 months after the last dose of study treatment, or according to the local guidelines for LEN, whichever is longer.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence and severity of TEAEs (TEAE, treatment-emergent adverse event)

Secondary endpoints 5

1. • Tafasitamab serum concentrations after 3 (Ctrough and Cmax) and 12 (Ctrough) treatment cycles
2. • Best Objective Response Rate (ORR) by Investigator assessment up to treatment Cycle 12 based on Cheson et al. (2007)
3. • Duration of Response (DoR) by Investigator assessment based on Cheson et al. (2007)
4. • Progression-Free Survival (PFS) by Investigator assessment based on Cheson et al. (2007)
5. • Number and percentage of patients developing anti- tafasitamab antibodies up to treatment Cycle 12

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Corp.

Sponsor organisation

Incyte Corp.

Address

1801 Augustine Cut Off

City

Wilmington

Postcode

19803-4404

Country

United States

Scientific contact point

Organisation

MorphoSys AG

Contact name

Medical Information

Public contact point

Organisation

MorphoSys AG

Contact name

Medical Information

Incyte Corp.

Sponsor organisation

Incyte Corp.

Address

1801 Augustine Cut Off

City

Wilmington

Postcode

19803-4404

Country

United States

Scientific contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Public contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Third parties 13

Locations

5 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 31 files

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

Application history

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