Refractory Follicular Lymphoma, Relapsed Follicular Lymphoma
Conditions
Keywords
Relapsed Follicular Lymphoma, Refractory Follicular Lymphoma, Loncastuximab Tesirine, Follicular Lymphoma, Lymphoma
Brief summary
This study aims to evaluate the efficacy of single agent loncastuximab tesirine compared to idelalisib in participants with relapsed or refractory follicular lymphoma.
Interventions
DRUGLoncastuximab Tesirine
IV infusion
DRUGIdelalisib
Oral tablet
Sponsors
ADC Therapeutics S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent must be obtained prior to any study procedures. * Male or female participants aged 18 years or older, with pathologic diagnosis of follicular lymphoma (FL) (Grade 1, 2, 3A) in the most recent tumor biopsy. * Relapsed or refractory disease following two or more treatment regimens, at least one of which must have contained an anti-CD20 therapy. * Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy. * Measurable disease as defined by the 2014 Lugano Classification as assessed by positron emission tomography - computed tomography (PET-CT) or, if not Fluorodeoxyglucose (FDG) avid, CT or magnetic resonance imaging (MRI). * Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available). Note: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. * Adequate organ function as defined by screening laboratory values within the following parameters: 1. Absolute neutrophil count (ANC) ≥1.0 × 10\^3/μL (off growth factors at least 72 hours), 2. Platelet count ≥75 × 10\^3/μL without transfusion in the past 2 weeks, 3. Alanine aminotransferase, AST, and GGT ≤2.5 × the upper limit of normal (ULN), 4. Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN), 5. Calculated creatinine clearance ≥30 mL/min by the Cockcroft and Gault equation. Note: A laboratory assessment may be repeated a maximum of two times during the Screening period to confirm eligibility * Women of childbearing potential (WOCBP)(1) must agree to use a highly effective method(2) of contraception from the time of giving informed consent until at least 9 months after the last dose of study treatment. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent until at least 6 months after the participant receives his last dose of study treatment. 1. WOCBP are defined as sexually mature women who have not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or who have not been postmenopausal. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 2. Highly effective forms of birth control are methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Highly effective forms of birth control include hormonal contraceptives associated with inhibition of ovulation (oral, injectable, patch, intrauterine devices), male partner sterilization, or total abstinence from heterosexual intercourse, when this is the preferred and usual lifestyle of the participant. Note: The double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal, post ovulation), withdrawal (coitus interruptus), lactational amenorrhea method, and spermicide-only are not acceptable as highly effective methods of contraception.
Exclusion criteria
* Previous treatment with loncastuximab tesirine. * Previous treatment with idelalisib. * History of hypersensitivity to any of the excipients of loncastuximab tesirine or idelalisib. * Follicular lymphoma which has transformed to diffuse large B-cell lymphoma (DLBCL) or other aggressive lymphomas. * Requires treatment or prophylaxis with a strong cytochrome P450 (CYP) 3A inhibitor, inducer, or sensitive substrate. * History of or ongoing drug-induced pneumonitis. * History of or ongoing inflammatory bowel disease. * Any condition that could interfere with the absorption or metabolism of idelalisib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. * Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary. * Autologous transplant within 30 days prior to start of study treatment (C1D1). * Allogenic transplant within 60 days prior to start of study treatment (C1D1). * Active graft-versus-host disease. * Post-transplantation lymphoproliferative disorders. * Human immunodeficiency virus (HIV) seropositive with any of the following: 1. CD4+ T-cell counts \<350 cells/μL. 2. Acquired immuno-deficiency syndrome (AIDS)-defining opportunistic infection within 12 months prior to screening. 3. Not on anti-retroviral therapy, or on anti-retroviral therapy for \< 4 weeks at the time of screening. 4. HIV viral load ≥400 copies/mL. * Serologic evidence of chronic hepatitis B infection and unable or unwilling to receive standard prophylactic anti-viral therapy or with detectable hepatitis B virus (HBV) viral load. * Serologic evidence of hepatitis C infection without completion of curative treatment or with detectable hepatitis C virus (HCV) viral load. * History of Stevens-Johnson syndrome or toxic epidermal necrolysis. * Lymphoma with active central nervous system involvement, including leptomeningeal disease. * Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath). * Breastfeeding or pregnant. * Significant medical comorbidities, including but not limited to, uncontrolled hypertension (BP ≥160/100 mm Hg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease. * Any Grade ≥3 active infection which requires IV antibiotics, IV antiviral, or IV antifungal treatment. * Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study treatment (C1D1), except shorter if approved by the Sponsor. * Use of any other experimental medication within 30 days prior to start of study treatment (C1D1). * Live vaccine administration within 4 weeks prior to Cycle(C) 1 Day (D) 1. * Failure to recover to ≤ Grade 1 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) from acute non-hematologic toxicity (except ≤Grade 2 neuropathy or alopecia) due to previous therapy prior to screening. * Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participant inappropriate for study participation or put the participant at risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) | Up to the end of treatment, maximum time on treatment was 333 days | CRR was defined as the percentage of participants who experienced a best overall response (BOR) of complete response (CR) assessed prior to any subsequent anticancer treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to end of treatment, maximum time on treatment was 333 days | PFS was defined as the time between the randomization date and the first documentation of recurrence, progression, or death. |
| Overall Survival (OS) | Up to end of treatment, maximum time on treatment was 333 days | OS was defined as the time between the randomization date and death from any cause. |
| Duration of Response (DOR) | Up to end of treatment, maximum time on treatment was 333 days | DOR was defined as the time from the documentation of tumor response to disease progression or death. |
| Average Concentration of Loncastuximab Tesirine at the End of Infusion | Up to end of treatment, maximum time on treatment was 333 days | — |
| Clearance Rate of Loncastuximab Tesirine | Up to end of treatment, maximum time on treatment was 333 days | — |
| Volume of Distribution of Loncastuximab Tesirine | Up to end of treatment, maximum time on treatment was 333 days | — |
| Overall Response Rate (ORR) | Up to end of treatment, maximum time on treatment was 333 days | ORR was defined as the percentage of participants with a BOR of CR or partial response (PR) assessed prior to any subsequent anticancer treatment. |
| Average Concentration of Loncastuximab Tesirine Before Infusion | Up to end of treatment, maximum time on treatment was 333 days | — |
| Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine | Up to end of treatment, maximum time on treatment was 333 days | — |
| Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) | Up to end of treatment, maximum time on treatment was 333 days | — |
| Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) | Up to end of treatment, maximum time on treatment was 333 days | — |
| Number of Participants With Specific Symptomatic Adverse Event Symptoms As Selected From Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Up to end of treatment, maximum time on treatment was 333 days | The specific symptomatic adverse events includes fatigue, swelling, rash, nausea, diarrhea, abdominal pain, and cough. |
| Treatment-Related Symptoms as Assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Up to end of treatment, maximum time on treatment was 333 days | The specific symptoms assessed include fatigue, swelling, rash, nausea, diarrhea, abdominal pain, and cough. The severity is assessed from None to Very severe and the interference level is assessed from Not at all to Very much. |
| Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | Day 1 to 30 days after end of treatment, maximum time on treatment was 333 days | TEAEs were defined as an AE that occurs or worsens in the period extending from the first dose of study treatment until 30 days after the last dose of study treatment or start of new anti-cancer therapy, whichever is earlier. Any clinically significant changes from baseline in the safety laboratory values, vital signs, 12-lead electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status were reported as TEAEs. |
Countries
Belgium, France, Hungary, Israel, Italy, Poland, Spain, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Loncastuximab Tesirine Participants were administered loncastuximab tesirine as an intravenous (IV) infusion on Day 1 of each cycle, where 1 cycle is 3 weeks. Loncastuximab tesirine was administered at a dose of 150 μg/kg for 2 cycles, then at a dose of 75 μg/kg for subsequent cycles.
The median number of treatment cycles was 5.5 (min: 5; max: 12). The median treatment duration was 122.5 days (min: 54; max: 231 days). | 4 |
| Idelalisib Participants were administered 150 mg idelalisib, orally, twice a day throughout each cycle, where 1 cycle is 4 weeks.
1 participant received 6 cycles and the other participant received 13 cycles of treatment. The treatment duration was 140 days and 333 days, respectively. | 2 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Radiographic progression | 0 | 1 |
| Overall Study | Study termination by sponsor | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Idelalisib | Total | Loncastuximab Tesirine |
|---|---|---|---|
| Age, Customized 55 to 69 years | 2 Participants | 6 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 0 / 2 |
| other Total, other adverse events | 4 / 4 | 2 / 2 |
| serious Total, serious adverse events | 3 / 4 | 0 / 2 |
Outcome results
Primary
Complete Response Rate (CRR)
CRR was defined as the percentage of participants who experienced a best overall response (BOR) of complete response (CR) assessed prior to any subsequent anticancer treatment.
Time frame: Up to the end of treatment, maximum time on treatment was 333 days
Population: No response data was collected.
Secondary
Average Concentration of Loncastuximab Tesirine at the End of Infusion
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No data was collected.
Secondary
Average Concentration of Loncastuximab Tesirine Before Infusion
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No data was collected.
Secondary
Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No data was collected.
Secondary
Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No data was collected.
Secondary
Clearance Rate of Loncastuximab Tesirine
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No data was collected.
Secondary
Duration of Response (DOR)
DOR was defined as the time from the documentation of tumor response to disease progression or death.
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No response data was collected.
Secondary
Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)
TEAEs were defined as an AE that occurs or worsens in the period extending from the first dose of study treatment until 30 days after the last dose of study treatment or start of new anti-cancer therapy, whichever is earlier. Any clinically significant changes from baseline in the safety laboratory values, vital signs, 12-lead electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status were reported as TEAEs.
Time frame: Day 1 to 30 days after end of treatment, maximum time on treatment was 333 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Loncastuximab Tesirine | Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | TEAEs | 4 Participants |
| Loncastuximab Tesirine | Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | Serious TEAEs | 3 Participants |
| Idelalisib | Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | TEAEs | 2 Participants |
| Idelalisib | Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE) | Serious TEAEs | 0 Participants |
Secondary
Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No data was collected.
Secondary
Number of Participants With Specific Symptomatic Adverse Event Symptoms As Selected From Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
The specific symptomatic adverse events includes fatigue, swelling, rash, nausea, diarrhea, abdominal pain, and cough.
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No data was collected.
Secondary
Overall Response Rate (ORR)
ORR was defined as the percentage of participants with a BOR of CR or partial response (PR) assessed prior to any subsequent anticancer treatment.
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No response data was collected.
Secondary
Overall Survival (OS)
OS was defined as the time between the randomization date and death from any cause.
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: Inclusive of participants who experienced death.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Loncastuximab Tesirine | Overall Survival (OS) | NA days |
Secondary
Progression-Free Survival (PFS)
PFS was defined as the time between the randomization date and the first documentation of recurrence, progression, or death.
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: Inclusive of participants who experienced recurrence, progression, or death.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Loncastuximab Tesirine | Progression-Free Survival (PFS) | NA days |
| Idelalisib | Progression-Free Survival (PFS) | NA days |
Secondary
Treatment-Related Symptoms as Assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
The specific symptoms assessed include fatigue, swelling, rash, nausea, diarrhea, abdominal pain, and cough. The severity is assessed from None to Very severe and the interference level is assessed from Not at all to Very much.
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No data was collected.
Secondary
Volume of Distribution of Loncastuximab Tesirine
Time frame: Up to end of treatment, maximum time on treatment was 333 days
Population: No data was collected.