Clinical trial NCT04661007: To Assess the Safety and Tolerability of Tafasitamab Alone or in Combination With Other Drugs in Japanese Participants With Non-Hodgkins Lymphoma (NHL)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non Hodgkins Lymphoma
Diffuse Large B-cell Lymphoma
Keywords: INCMOR00208
tafasitamab
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2020-12-09
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter study to evaluate safety and tolerability, determine the RP2Ds of tafasitamab alone in Japanese participants with R/R NHL, or to evaluate efficacy and safety of tafasitamab in combination with lenalidomide in Japanese participants with R/R DLBCL, or tafasitimab in combination with lenalidomide plus R-CHOP in Japanese participants with previously untreated DLBC, or tafasitimab in combination with lenalidomide in Japanese participants with previously R/R DLBC.


Eligibility criteria: Inclusion Criteria:

* Group 1 only: Biopsy-proven participants with relapsed or refractory NHL of DLBCL, FL or MZL.
* Groups 3, 4a and 5 only: Biopsy-proven participants with relapsed or refractory DLBCL.
* Groups 2 and 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 as defined in the protocol.
* Group 1 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 2, 3, 4a and 6 only:

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: Participants must have:

  1. Untreated DLBCL.
  2. Ann Arbor Stage III to IV.
  3. IPI status of 3 to 5 or age-adjusted IPI 2-3 (in Group 5 only).
  4. Appropriate candidate for R-CHOP.
  5. LVEF of ≥ 50%, assessed by echocardiography.
* Willingness to avoid pregnancy or fathering children.
* In the opinion of investigator, the participant must:

  1. Not have a history of noncompliance in relation to medical regimens or be considered potentially unreliable and/or uncooperative.
  2. 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.
* 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 investigator's opinion preclude participation in the study or compromise the participant's 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 2, 3, 4a, 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 2, 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
* Group 4a 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, 3, 4a and 6 only: Participants who have:

  1. Not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy, or other lymphoma-specific therapy within the 14 days prior to Day 1 dosing.
  2. In the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies.
  3. Groups 1, 3 and 4a only: Previous treatment with CD19-targeted therapy (eg, CD19-CAR-T therapies, other CD19 mAbs including bispecific and ADCs).

     Groups 2 and 6 only: Previous treatment with tafasitamab. Note: Participants in Groups 2 and 6 who have received previous CD19 directed therapy (other than tafasitamab) must have CD19-positive lymphoma confirmed by a biopsy taken after completing the prior CD19-targeted therapy.
  4. Groups 2, 3 and 6 only: Been previously treated with IMiDs (eg, thalidomide or LEN).
  5. Group 4a only: Been previously treated with selective PI3Kδ or pan-PI3K inhibitors (eg, idelalisib, copanlisib, duvelisib) and/or Bruton's tyrosine kinase inhibitors (eg, ibrutinib).
  6. 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).
  7. 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.
  8. Undergone previous allogenic stem cell transplantation.
  9. Concurrent treatment other anticancer or experimental treatments.
* Group 5 only: Participants who have:

  1. A history of radiation therapy to ≥ 25% of the bone marrow for other diseases or history of anthracycline therapy.
  2. A history of hypersensitivity or contraindication to any component of R-CHOP, LEN, or compounds of similar biological or chemical composition as tafasitamab and/or the excipients contained in the study treatment formulations or R-CHOP.
  3. Contraindication to any of the individual components of R-CHOP.
  4. Any anticancer and/or investigational therapy within 30 days prior to the start of Cycle 1, except for permitted prephase treatment defined below.

Primary outcomes:
measure: Part 1,2 and 3 : Treatment Emergent Adverse Events (TEAE'S)
timeFrame: Approximately 2 years
measure: Part 4: Objective Response
timeFrame: Approximately 27 months
Secondary outcomes:
measure: Part 1,2, 3 and 4 : Cmax of tafasitamab
timeFrame: Approximately 27 months
measure: Part 1, 2, 3 and 4: Cmin of tafasitamab
timeFrame: Approximately 27 months
measure: Part 4: Complete Response
timeFrame: Approximately 27 months
measure: Part 4: Duration of Response
timeFrame: Approximately 27 months
measure: Part 4: Progression-Free Survival
timeFrame: Approximately 27 months
measure: Part 4: Overall Survival
timeFrame: Approximately 27 months
measure: Part 4: Overall Response Rate
timeFrame: Approximately 27 months
measure: Part 4: Treatment Emergent Adverse Events (TEAE'S)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Fukui
country: Japan
facility: University of Fukui Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hyogo
country: Japan
facility: Kobe City Medical Center General Hospital
city: Kanagawa
country: Japan
facility: Tokai University Hospital
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Jfcr
city: Kumamoto-ken
country: Japan
facility: Nho Kumamoto Medical Center
city: Matsuyama
country: Japan
facility: Nho Shikoku Cancer Center
city: Miyagi
country: Japan
facility: Tohoku University Hospital
city: Nagoya
country: Japan
facility: Japanese Red Cross Nagoya Daini Hospital
city: Narita City
country: Japan
facility: Iuhw Narita Hospital
city: Okayama
country: Japan
facility: Nho Okayama Medical Center
city: Osakasayama City
country: Japan
facility: Kindai University Hospital
city: Saitama-shi
country: Japan
facility: Saitama Medical Center
city: Sapporo
country: Japan
facility: Nho Hokkaido Cancer Center
city: Suita-shi
country: Japan
facility: Osaka University Hospital
city: Tachikawa
country: Japan
facility: Nho Disaster Medical Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: TSU
country: Japan
facility: Mie University Hospital
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
Study officials:
References: