Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Loncastuximab Tesirine · 9 trials · 17 indications
To evaluate the efficacy of SOC CAR T-cell therapy in patients with R/R large B-cell lymphoma following bridging with lonca-R.
To evaluate toxicities post CAR-T
To evaluate toxicities post CAR-T
To evaluate toxicities post CAR-T
Evaluated per 2014 Lugano criteria. An exact 95% confidence interval will be calculated.
Overall Response Rate= Minor response (\>25%-50% reduction in serum IgM from baseline) + Partial Response (\>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (\>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).
Complete Response rate will be reported as the number of participants achieving complete response (CR) to study therapy. Response to therapy will be assessed using Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) (FDG-PET)/ Computerized Tomography (CT) following Lugano 2014 criteria by week 12 of treatment.
ORR, as determined by central review according to the 2014 Lugano classification, defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR).
To assess the Recommended Phase 2 Dose (RP2D) of loncastuximab tesirine and rituximab in participants with post-transplant lymphoproliferative disorders (PTLD).
To assess the efficacy of the combination of lonca-R based on CR rate after 4 cycles.
Frequency and severity of TEAEs and treatment-emergent serious adverse events (TESAEs). TEAEs and TESAEs will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
ECOG performance status will be measured on a scale from grades 0-5, where a higher grade indicates a worse outcome.
| Arm | Type | Description |
|---|---|---|
| Part 1: Loncastuximab Tesirine + Rituximab (Lonca-R) | EXPERIMENTAL | Part 1 consists of a non-randomized safety run-in period evaluating the study drug for the first 20 participants. Participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m\^2 Q3W for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m\^2 Q3W for up to 6 additional cycles. |
| Part 2: Loncastuximab Tesirine + Rituximab (Lonca-R) | EXPERIMENTAL | Randomized participants will receive Lonca-R on Day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R will be administered via an intravenous infusion of loncastuximab tesirine 150 µg/kg + rituximab 375 mg/m\^2 every Q3W for 2 cycles, then loncastuximab tesirine 75 µg/kg + rituximab 375 mg/m\^2 Q3W for up to 6 additional cycles. |
| Part 2: Standard Immunochemotherapy (R-GemOx) | ACTIVE_COMPARATOR | Randomized participants will receive R-GemOx consisting of rituximab, gemcitabine and oxaliplatin as a standard immunochemotherapy treatment on Day 1 or Day 2 of each cycle for up to 8 cycles, where 1 Cycle is 2 weeks. R-GemOx will be administered via an intravenous infusion of rituximab 375 mg/m\^2 + gemcitabine 1000 mg/m\^2 + oxaliplatin 100 mg/m\^2 every 2 weeks (Q2W) for up to 8 cycles. |
| Treatment: All Patients | EXPERIMENTAL | The study will investigate the effectiveness of Loncastuximab tesirine and Rituximab (Lonca-R) prior to standard of care CAR-T cell therapy. |
| Treatment (Lonca-R, DA-EPOCH-R) | EXPERIMENTAL | Patients receive rituximab IV, loncastuximab tesirine IV, etoposide IV, doxorubicin IV, vincristine IV, prednisone PO, and cyclophosphamide IV on study. Patients also undergo collection of blood samples and bone marrow aspiration and biopsy at screening and CT or PET/CT at screening, throughout the study, and during follow up. |
| Loncastuximab Tesirine + Dexamethasone | EXPERIMENTAL | Participants will be given * Loncastuximab Tesirine on Day 1 of every 28 day study cycle and continue for up to 6 cycles. Participants will also receive pre-medications to reduce the chance of having a sensitivity reaction to the study treatment. Participants who tolerate the study treatment without a reaction may have pre-medications changed per determination of their doctor. * Dexamethasone will be given prior to study treatment on Day -1 or up to 2 hours prior to loncastuximab tesirine and the day after treatment |
| Loncastuximab tesirine + Rituximab | EXPERIMENTAL | During the 12-week Induction Phase (Cycles 1 to 4), participants will receive loncastuximab tesirine on days 1 of each 3-week cycle for Cycles 1 through 4; and rituximab on days 1, 8, 15 of Cycle 1 and day 1 of Cycle 2. Maintenance Phase 1 (Cycle 5) is 8 weeks: Participants achieving complete response (CR) or partial response (PR) during the Induction Phase will receive loncastuximab tesirine once every 3-weeks; and rituximab once during week 7 or 8. Participants achieving a response of Stable Disease (SD) or Progressive Disease (PD) will be taken off treatment. Maintenance Phase 2 (Cycles 6 and 7) is 16 weeks: * Participants achieving CR during Maintenance Phase 1 receive rituximab once during week 7 or 8 of Cycles 6 and 7. * Participants achieving PR during Maintenance Phase 1 receive loncastuximab tesirine once every 3-weeks over each 8 week cycle; and rituximab once during week 7 or 8 of Cycles 6 and 7. * Participants achieving SD or PD will be taken off treatment. |
| Loncastuximab tesirine | EXPERIMENTAL | Participants will receive loncastuximab tesirine as an IV infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg Q3W for 2 cycles, then 75 μg/kg Q3W for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first. |
| Dose Level 1 (starting dose): SD or PD | EXPERIMENTAL | Dose Level 1: * Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks * Rituximab: 375 mg/m2 IV This arm included participants who had SD (Stable Disease) or PD (Progressive Disease) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they do not achieve a response, they will come off the study but will be monitored for survival. |
| Dose Level 1 (starting dose): PR | EXPERIMENTAL | Dose Level 1: * Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks * Rituximab: 375 mg/m2 IV This arm included participants who had a Partial Response (PR) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve PR, they will have the option to receive either rituximab consolidation or R-CHOP (at the physician's discretion). |
| Dose Level 1 (starting dose): CR | EXPERIMENTAL | Dose Level 1: * Loncastuximab tesirine: 0.075 mg/kg IV every 3 weeks * Rituximab: 375 mg/m2 IV This arm included participants who had a Complete Response (CR) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve a CR after 4 cycles of Lonca-R, they will receive rituximab consolidation (SOC). |
| Dose Level 2: SD or PD | EXPERIMENTAL | Dose Level 2: * Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3 * Rituximab: 375 mg/m2 IV This arm included participants who had SD (Stable Disease) or PD (Progressive Disease) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they do not achieve a response, they will come off the study but will be monitored for survival. |
| Dose Level 2: PR | EXPERIMENTAL | Dose Level 2: * Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3 * Rituximab: 375 mg/m2 IV This arm included participants who had a Partial Response (PR) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve PR, they will have the option to receive either rituximab consolidation or R-CHOP (at the physician's discretion). |
| Dose Level 2: CR | EXPERIMENTAL | Dose Level 2: * Loncastuximab tesirine: 0.15 mg/kg IV every 3 weeks for the first 2 cycles, then 0.075 mg/kg starting C3 * Rituximab: 375 mg/m2 IV This arm included participants who had a Complete Response (CR) after the first 6 weeks of treatment. Lonca-R will be administered for 4 cycles with response assessment at 6 weeks (+/- 1 week) following the last Lonca-R treatment. If they achieve a CR after 4 cycles of Lonca-R, they will receive rituximab consolidation (SOC). |
| Arm A: Normal Hepatic Function | EXPERIMENTAL | Participants will receive loncastuximab tesirine 0.15 mg/kg once every 3 weeks (Q3W) for two cycles, then 0.075 mg/kg Q3W for subsequent cycles (1 cycle = 21 days). Participants who have a toxicity meeting the criteria for dose reduction will have subsequent doses reduced by 50%. If the toxicity recurs, subsequent doses must be reduced by an additional 50%. A maximum of 2 dose reductions are allowed. Participants who have a toxicity meeting the criteria for dose reduction following Cycle 2 will receive the protocol-specified dose of 50% of initiate dose for Cycle 3, i.e., they will not have an additional dose reduction for Cycle 3. |
| Arm B: Moderate Hepatic Impairment | EXPERIMENTAL | Participants will receive loncastuximab tesirine in a standard 3+3 dose-escalation design. Initial dose will be 0.09 mg/kg Q3W for two cycles, then 0.045 mg/kg Q3W for subsequent cycles (1 cycle = 21 days). The highest dose possibly administered will be 0.15 mg/kg Q3W. Participants who have a toxicity meeting the criteria for dose reduction will have subsequent doses reduced by 50%. If the toxicity recurs, subsequent doses must be reduced by an additional 50%. A maximum of 2 dose reductions are allowed. Participants who have a toxicity meeting the criteria for dose reduction following Cycle 2 will receive the protocol-specified dose of 50% of initiate dose for Cycle 3, i.e., they will not have an additional dose reduction for Cycle 3. |
| Arm C: Severe Hepatic Impairment | EXPERIMENTAL | Participants will receive loncastuximab tesirine in a standard 3+3 dose-escalation design. Initial dose will be 0.09 mg/kg Q3W for two cycles, then 0.045 mg/kg Q3W for subsequent cycles (1 cycle = 21 days). The highest dose possibly administered will be 0.15 mg/kg Q3W. Participants who have a toxicity meeting the criteria for dose reduction will have subsequent doses reduced by 50%. If the toxicity recurs, subsequent doses must be reduced by an additional 50%. A maximum of 2 dose reductions are allowed. Participants who have a toxicity meeting the criteria for dose reduction following Cycle 2 will receive the protocol-specified dose of 50% of initiate dose for Cycle 3, i.e., they will not have an additional dose reduction for Cycle 3. |
| Part 1 (Dose Escalation): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C) | EXPERIMENTAL | Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on Day (D) 1 of each cycle (where each cycle is 21 days). Participants will also receive polatuzumab vedotin at a dose of 1.8 mg/kg on D1 of each cycle, infusion will be started one hour after end of loncastuximab tesirine infusion. |
| Part 1 (Dose Escalation): Loncastuximab Tesirine + Glofitamab (Arm E) | EXPERIMENTAL | Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on D2 of Cycle (C) 1 and then D1 of all other cycles (where each cycle is 21 days). Participants will also receive glofitamab 2.5 mg on C1 D8, 10 mg on C1 D15 and 30 mg for cycles 2-12 D1. In addition participants will receive obinutuzumab pre-treatment 1000 mg on C1 D1. |
| Part 1 (Dose Escalation): Loncastuximab Tesirine + Mosunetuzumab (Arm F) | EXPERIMENTAL | Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on Day (D) 1 of each cycle (where each cycle is 21 days). Participants will also receive mosunetuzumab 5 mg on C1 D1, 45 mg for C1 D8, C1 D15 and cycles 2-8 D1. |
| Part 2 (Dose Expansion): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C) | EXPERIMENTAL | Participants with B-NHL will receive loncastuximab tesirine in combination with polatuzumab vedotin at the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) if favorable results of Part 1 are received. |
| Part 2 (Dose Expansion): Loncastuximab Tesirine + Glofitamab (Arm E) | EXPERIMENTAL | Participants with B-NHL will receive loncastuximab tesirine in combination with glofitamab at the MTD and/or RDE if favorable results of Part 1 are received. In addition participants will receive obinutuzumab pre-treatment 1000 mg on C1 D1. |
| Part 2 (Dose Expansion): Loncastuximab Tesirine + Mosunetuzumab (Arm F) | EXPERIMENTAL | Participants with B-NHL will receive loncastuximab tesirine in combination with mosunetuzumab at the MTD and/or RDE if favorable results of Part 1 are received. |
| Name | Type | Description |
|---|---|---|
| Loncastuximab Tesirine | DRUG | Intravenous Infusion |
| Rituximab | DRUG | Intravenous Infusion |
| Gemcitabine | DRUG | Intravenous Infusion |
| Oxaliplatin | DRUG | Intravenous Infusion |
| Cyclophosphamide | DRUG | Given IV |
| Doxorubicin | DRUG | Given IV |
| Etoposide | DRUG | Given IV |
| Prednisone | DRUG | Given PO |
| Vincristine | DRUG | Given IV |
| Dexamethasone | DRUG | Taken orally or administered by intravenous infusion |
| Rituximab or rituximab biosimilar | DRUG | Rituximab or rituximab biosimilar will be administered by IV at 375 mg/m2 on Day 1 of every cycle. Lonca will be administered first, followed by rituximab (with a 30 min wait time between the two agents) |
| Polatuzumab Vedotin | DRUG | IV infusion |
| Glofitamab | DRUG | IV infusion |
| Mosunetuzumab | DRUG | Subcutaneous (SC) injection |
| Obinutuzumab | DRUG | IV infusion |
Inclusion Criteria: * Male or female participant aged 18 years or older * Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization classification (including participants with DLBCL transformed from indolent lymphoma), or high-grade B-cell lymphoma, with MYC and BCL2 and/or BC...