Phase II Study to Assess AFM13 in Patients With R/R CD30-positive T-cell Lymphoma or Transformed Mycosis Fungoides (REDIRECT)

• ClinicalTrials.gov Identifier: NCT04101331
• Recruitment Status: Completed
• First Posted: September 24, 2019
• Results First Posted: June 5, 2023
• Last Update Posted: February 2, 2024
• Sponsor: Affimed GmbH
• Information provided by (Responsible Party): Affimed GmbH

Tracking Information

• First Submitted Date: September 20, 2019
• First Posted Date: September 24, 2019
• Results First Submitted Date: May 8, 2023
• Results First Posted Date: June 5, 2023
• Last Update Posted Date: February 2, 2024
• Actual Study Start Date: November 13, 2019
• Actual Primary Completion Date: May 11, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 8, 2023)

Overall Response Rate Assessed by Independent Review Committee Based on PET-CT [ Time Frame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 28 months). ]

Overall response by Positron Emission Tomography-Computed Tomography (PET-CT) as defined by achieving complete response and/or partial response assessed by an Independent Review Committee (IRC) utilizing the modified Lugano Classification Revised Staging System for malignant lymphoma (Cheson, 2014).

Original Primary Outcome Measures (submitted: September 23, 2019)

Antitumor activity of AFM13: Independent Review Committee (IRC)-confirmed objective response rate (ORR) [ Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]

Assessed by the modified Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) and after at least 8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF)

Current Secondary Outcome Measures (submitted: May 8, 2023)

• Overall Response Rate Assessed by Investigator Based on PET-CT [ Time Frame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 28 months). ]
  Overall response by Positron Emission Tomography-Computed Tomography (PET-CT) as defined by achieving complete response and/or partial response assessed by the investigator utilizing the modified Lugano Classification Revised Staging System for malignant lymphoma (Cheson, 2014).
• Overall Response Rate Assessed by Investigator Based on CT [ Time Frame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 28 months). ]
  Overall response by Computed Tomography (CT) as defined by achieving complete response and/or partial response assessed by the investigator utilizing the modified Lugano Classification Revised Staging System for malignant lymphoma (Cheson, 2014).
• Complete Response Rate and Partial Response Rate Assessed by Independent Review Committee Based on PET-CT [ Time Frame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 28 months). ]
  Complete response and/or partial response by Positron Emission Tomography-Computed Tomography (PET-CT) assessed by an Independent Review Committee (IRC) utilizing the modified Lugano Classification Revised Staging System for malignant lymphoma (Cheson, 2014).
• Complete Response Rate, Partial Response Rate and Overall Response Rate Assessed by Independent Review Committee Based on CT [ Time Frame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 28 months). ]
  Overall response by Computed Tomography (CT) as defined by achieving complete response and/or partial response assessed by an Independent Review Committee (IRC) utilizing the modified Lugano Classification Revised Staging System for malignant lymphoma (Cheson, 2014).
• Duration of Overall Response Assessed by Independent Review Committee Based on PET-CT [ Time Frame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 26 months). ]
  Duration of response (DOR) defined as the period from first Partial Response (PR) and Complete Response (CR) assessment till first assessment of progressive disease or death. Response assessed by Positron Emission Tomography-Computed Tomography (PET-CT) by Independent Review Committee (IRC).
• Duration of Overall Response Assessed by Independent Review Committee Based on CT [ Time Frame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 26 months). ]
  Duration of response (DOR) defined as the period from first Partial Response (PR) and Complete Response (CR) assessment till first assessment of progressive disease or death. Response assessed by Computed Tomography (CT) by Independent Review Committee (IRC).
• Duration of Overall Response Assessed by Investigator Based on PET-CT [ Time Frame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 26 months). ]
  Duration of response (DOR) defined as the period from first Partial Response (PR) and Complete Response (CR) assessment till first assessment of progressive disease or death. Response assessed by Positron Emission Tomography-Computed Tomography (PET-CT) by the investigator.
• Duration of Overall Response Assessed by Investigator Based on CT [ Time Frame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 26 months). ]
  Duration of response (DOR) defined as the period from first Partial Response (PR) and Complete Response (CR) assessment till first assessment of progressive disease or death. Response assessed by Computed Tomography (CT) by the investigator.
• Number of Subjects With Treatment Related Adverse Event [ Time Frame: From the date of first treatment until the date of the last treatment + 37 days, up to 138 weeks. ]
  Number of subjects who had treatment (AFM13) related Adverse Events.
• Maximum Measured Concentration (Cmax) of AFM13 [ Time Frame: Predose and 1 hour after start of infusion, end of injection (EOI) and 1 hour, 2 hours, 3 hours, 24 hours and 48 hours after EOI on Cycle 1 Day 1 and Day 29. ]
  Maximum measured concentration (Cmax) of the AFM13 in plasma.
• Area Under the Concentration-Time Curve of AFM13 From 0 to Infinity (AUC 0-∞) [ Time Frame: Predose and 1 hour after start of infusion, end of injection (EOI) and 1 hour, 2 hours, 3 hours, 24 hours and 48 hours after EOI on Cycle 1 Day 1 and Day 29. ]
  Area under concentration (AUC) versus time curve of the AFM13 in plasma over time interval from 0 extrapolated to infinity.
• Volume of Distribution at Steady State (Vss) of AFM13 [ Time Frame: Predose and 1 hour after start of infusion, end of injection (EOI) and 1 hour, 2 hours, 3 hours, 24 hours and 48 hours after EOI on Cycle 1 Day 1 and Day 29. ]
  Volume of distribution at steady state (Vss) of the AFM13.
• The Terminal Half-life (t1/2) of AFM13 [ Time Frame: Predose and 1 hour after start of infusion, end of injection (EOI) and 1 hour, 2 hours, 3 hours, 24 hours and 48 hours after EOI on Cycle 1 Day 1 and Day 29. ]
  The terminal half-life (t1/2) of the AFM13.
• European Quality of Life 5-dimensional Pain/Discomfort Score (EQ-5D) [ Time Frame: At baseline and final study visit, up to 138 weeks. ]
  Quality of Life (QoL) as measured by the European QoL 5-dimensional questionnaire (EQ-5D) for Cohorts A. The EQ-5D comprises asks for the current health state in the five dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Pain/discomfort scores assessed based on questionnaire. The categories of the response offer three levels pain/discomfort score: "no pain or discomfort" (score of 1), "moderate pain or discomfort" (score of 2), and "extreme pain and discomfort" (score of 3). Scores are presented from baseline to each visit for Cohort A.
• European Quality of Life 5-dimensional Visual Analogue Scale Scores (EQ-5D) [ Time Frame: From baseline until final study visit, up to 138 weeks. ]
  Quality of Life (QoL) as measured by the European Quality of Life 5-dimensional questionnaire (EQ-5D) for Cohorts A. Visual Analogue Scale scores assessed based on drawn scale from 0(worst imaginable state) to 100(best imaginable state). Subjects chose their health state on scale based on their situation by themselves.

Original Secondary Outcome Measures (submitted: September 23, 2019)

• Antitumor activity of AFM13: Investigator-assessed objective response rate (ORR-2) [ Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
  Assessed by the modified Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) and after at least 8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF)
• Duration of response to AFM13 (DOR) [ Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
  Assessed by the modified Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) and after at least 8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF )
• Safety of AFM13 [ Time Frame: From screening till final study visit (30-37 days after last dose) ]
  Number and frequency of Adverse Events, which includes clinical significant abnormal findings in safety laboratory, vital signs and ECG assessments.
• Pharmacokinetics (PK) of AFM13 [ Time Frame: During Cycle 1 (each cycle is 56 days) ]
  Cmax (maximum measured concentration of the analyte in plasma)
• PK of AFM13 [ Time Frame: During Cycle 1 (each cycle is 56 days) ]
  AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
• PK of AFM13 [ Time Frame: During Cycle 1 (each cycle is 56 days) ]
  Vss (Volume of distribution at steady state)
• PK of AFM13 [ Time Frame: During Cycle 1 (each cycle is 56 days) ]
  t1/2 (Terminal half-life)
• Immunogenicity of AFM13 [ Time Frame: From screening till final study visit (30-37 days after last dose) ]
  Maximum change from baseline of anti-drug antibodies (ADA) in blood and their neutralizing potential
• Quality of Life (QoL) [ Time Frame: Through study completion, up to 12 months ]
  QoL as measured by the European Quality of Life 5-dimensional questionnaire (EQ-5D) for Cohorts A and B; and by Skindex-29 for Cohort C

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase II Study to Assess AFM13 in Patients With R/R CD30-positive T-cell Lymphoma or Transformed Mycosis Fungoides
• Official Title: A Phase II Open-label Multicenter Study to Assess the Efficacy and Safety of AFM13 in Patients With Relapsed or Refractory CD30-positive Peripheral T-cell Lymphoma or Transformed Mycosis Fungoides (REDIRECT)

Brief Summary

This is a phase II study to evaluate the antitumor activity and safety of AFM13 given as monotherapy in patients with CD30-positive T-cell lymphoma. The investigational medicinal product AFM13 is a tetravalent bispecific chimeric (anti-human CD30 x anti-human CD16A) recombinant antibody construct which is being developed to treat CD30-positive malignancies.

Patients who suffer from peripheral T-cell lymphoma or transformed mycosis fungoides, whose tumor expresses the surface marker CD30, and who have relapsed after an earlier treatment or have refractory disease will be enrolled into this study if all of the study entry criteria are fulfilled. Dependent on their disease type and the magnitude of CD30 expression, study participants will be assigned to one of 3 study cohorts, each cohort receiving the same treatment of weekly AFM13 infusions (a 200mg dose per infusion).

The main goal of the study is to assess the efficacy of AFM13 treatment as judged by the rate of overall responses. Further goals are to assess the safety of AFM13 treatment, the immunogenicity of AFM13 (as measured by the potential formation of anti-AFM13 antibodies) and the concentration of AFM13 in the blood.

Approx. 1 month after the last dose of AFM13 there will be a final study visit to assess the patients' health status after therapy, followed by quarterly phone contacts to check on their overall health status and long-term survival.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Peripheral T Cell Lymphoma
• Transformed Mycosis Fungoides

Intervention

Drug: AFM13

weekly intravenous infusions of 200mg

Study Arms

Experimental: Cohort A

Subjects with Relapsed or Refractory CD30 positive Peripheral T-cell Lymphoma (PTCL).

Intervention: Drug: AFM13

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 8, 2023): 108
• Original Estimated Enrollment (submitted: September 23, 2019): 145
• Actual Study Completion Date: January 11, 2024
• Actual Primary Completion Date: May 11, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Main Inclusion Criteria:

• Histologically confirmed CD30-positive PTCL (most subtypes allowed) or TMF per the revised World Health Organization 2016 classification (Swerdlow, 2016) by central assessment.
• Cohorts A and B (PTCL cohorts): measurable by the modified Lugano Classification (Cheson, 2014); measurable disease of ≥1.5 cm diameter by computed tomography (CT), assessed locally for eligibility. Note: fluorodeoxyglucose (FDG) avid disease by positron emission tomography (PET) recommended, if possible.
• Cohort C (TMF cohort): measurable by the Olsen Criteria (Olsen, 2011) including at least 1 cutaneous lymphoma lesion ≥2 cm in diameter, assessed locally for eligibility.
• Patients must have relapsed or refractory disease AND the following:
• Cohorts A and B (PTCL): patients must have received at least 1 prior line of systemic therapy. For patients with systemic ALCL, patients must have failed or be intolerant to brentuximab vedotin [BV]; Adcetris®
• Cohort C (TMF): patients must have received at least 1 prior line of systemic therapy; and have exhausted systemic therapies with regular approval for their disease

Main Exclusion Criteria:

• Patients with the following subtypes of lymphoma: T-cell prolymphocytic leukemia; T-cell large granular lymphocytic leukemia; Chronic lymphoproliferative disorder of NK cells; Aggressive NK-cell leukemia; Extranodal NK-/T-cell lymphoma; Indolent T-cell lymphoproliferative disorder of the GI tract:
• Has had an allogenic tissue hematopoietic cell/solid organ transplant within the last 3 years. Note: Patients who have had a transplant >3 years ago are eligible as long as there are no signs/symptoms of graft versus host disease (GvHD).
• Requirement for systemic immunosuppressive therapy, e.g. GvHD therapy, <12 weeks prior to the first dose of study drug.
• Prior treatment with AFM13

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Germany, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Turkey, United States

Administrative Information

• NCT Number: NCT04101331
• Other Study ID Numbers: AFM13-202
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Affimed GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: Affimed GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Karenza Alexis, MD; Affimed Inc.
• Principal Investigator: Won Seog Kim, Dr; Samsung Medical Center
• Principal Investigator: Steven Horwitz, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Affimed GmbH
• Verification Date: August 2023