A Phase 1b/2 Study of Tafasitamab, Tafasitamab Plus Lenalidomide, Tafasitamab Plus Parsaclisib, and Tafasitamab Plus Lenalidomide in Combination With R-CHOP in Japanese Participants With Non-Hodgkin Lymphoma

Phase 1

Recruiting

• Conditions: on Hodgkins Lymphoma, Diffuse Large B-cell Lymphoma

• Registration Number: JPRN-jRCT2031200357
• Lead Sponsor: eda Eiji

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-02-12
• Last Update Posted: 17 October 2023

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

Groups 1 and 2 only: Biopsy-proven participants with relapsed or refractory NHL of DLBCL, FL or MZL.
- Groups 3, and 4 only: Biopsy-proven participants with relapsed or refractory DLBCL.
- Groups 5 only: Biopsy-proven participants with relapsed or refractory DLBCL.
- Group 6 only: Biopsy-proven participants with DLBCL and another select lymphoid neoplasms.
- Participants must have at least 1 bi-dimensionally measurable lesion.
- ECOG performance status of 0 to 2.
- Participants with protocol defined laboratory criteria at screening
- Groups 1 and 2 only:
Received at least 1 previous systemic therapy line for the treatment of NHL. At least 1 previous therapy line must have included a CD20-targeted therapy (eg, RTX).
- Groups 3, 4a, and 4b and 6only:
Received at least 1, but no more than 3, previous systemic therapy lines for the treatment of DLBCL. At least 1 previous therapy line must have included a CD20-targeted therapy (eg, RTX).
- Group 5 only:
Participant must have:
a. Untreated DLBCL.
b. Ann Arbor Stage III to IV.
c. IPI status of 3 to 5 or age-adjusted IPI 2-3 (in Group 5 only).
d. Appropriate candidate for R-CHOP.
e. LVEF of >=50%, assessed by echocardiography.
- Willingness to avoid pregnancy or fathering children.
- In the opinion of investigator, the participant must:
a. Not have a history of noncompliance in relation to medical regimens or be considered potentially unreliable and/or uncooperative.
b. Be able to understand the reason for complying with the special conditions of the pregnancy prevention risk management plan and give written acknowledgement of this.

Exclusion Criteria

- Any other histological type of lymphoma
- Group 6 only: Primary refractory DLBCL
- History of prior non-hematologic malignancy
- Congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
- Participants with known positive test result for hepatitis C, and hepatitis B.
- Known seropositive for or history of active viral infection with HIV.
- Known active bacterial, viral, fungal, mycobacterial, or other infection at screening.
- Known CNS lymphoma involvement-present or past medical history.
- History or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigators opinion preclude participation in the study or compromise the participants ability to give informed consent.
- History or evidence of rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
- History or evidence of interstitial lung disease.
- Vaccination with live vaccine within 21 days prior to study treatment (Note: throughout the study treatment period and at least 6 months after end of treatment, vaccination with live vaccines should be avoided).
- Major surgery within up to 30 days prior to signing the ICF, unless the participant is recovered at the time of signing the ICF.
- Any anticancer and/or investigational therapy within 14 days prior to the start of Cycle 1
- Groups 3, 4a, 4b, 5 and 6 only: Gastrointestinal abnormalities including the inability to take oral study treatment, requiring IV alimentation, or prior surgical procedure affecting absorption.
- Pregnancy or lactation.
- Groups 3, 5 and 6 only: Participants who have history of deep venous thrombosis/embolism, threatening thromboembolism, stroke or known thrombophilia or are at a high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period if required
- Groups 4a and 4b only: Use or expected use during the study of any restricted medications, including potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer) before the date of study treatment administration.
- Groups 1, 2, 3, 4a, and 4b only: Participants who have:
a. Not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy, or other lymphoma-specific therapy within the 14 days prior to Day 1 dosing.
b. In the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies.
c. Previous treatment with CD19-targeted therapy (eg, CD19-CAR-T therapies, other CD19 mAbs including bispecific and ADCs).
d. Group 3 only: Been previously treated with IMiDs (eg, thalidomide or LEN).
e. Group 4a and 4b only: Been previously treated with selective PI3Kdelta or pan-PI3K inhibitors (eg, idelalisib, copanlisib, duvelisib) and/or Bruton's tyrosine kinase inhibitors (eg, ibrutinib).
f. 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 (citric acid monohydrate, polysorbate 20, sodium citrate dehydrate and trehalose dihydrate).
g. Undergone ASCT within the period <= 3 months before the signing of the ICF. Participants who have a more distant history of ASCT must exhibit full hematological recovery before enrolment into the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
- Part 1,2 and 3 : Treatment Emergent Adverse Events (TEAE'S)<br>- Part 4: Objective Response

Secondary Outcome Measures

Name	Time	Method
- Part 1,2, 3 and 4 : Cmax of tafasitamab<br>- Part 1, 2, 3 and 4 : Cmin of tafasitamab<br>- Part 4: Complete Response<br>- Part 4: Duration of Response<br>- Part 4: Progression-Free Survival<br>- Part 4: Overall Survival<br>- Part 4: Overall Response Rate<br>- Part 4: Treatment Emergent Adverse Events (TEAE'S)