Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication EPKINLY is a bispecific CD20-directed CD3 T-cell engager indicated: For the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy. FDA label
Also known as Epcoritamab (monotherapy), Epkinly, DuoBody-CD3xCD20, Epcoritamab-bysp, GEN 3013, Tepkinly, DuoBody®-CD3×CD20, ABBV-GMAB-3013
Epcoritamab · 29 trials · 79 indications
PFS is defined as the duration from the date of randomization to the date of disease progression determined per Lugano 2014 criteria as assessed by an independent review committee (IRC), or death, whichever occurs first.
CR30 will be determined by positron emission tomography-computerized tomography (cat scan) \[PET-CT\] per Lugano 2014 criteria, as assessed by independent review committee (IRC).
PFS is defined as the time from randomization until disease progression determined by Lugano 2014 criteria per IRC, or death, whichever occurs first.
PFS is defined as the duration from randomization to the date of disease progression as determined by Lugano 2014 criteria as assessed by Independent Review Committee (IRC), or death due to any cause whichever comes first.
BOR is defined as Complete Response (CR) or Partial Response (PR), determined by Lugano criteria, as assessed by an IRC.
PFS is defined as duration from the date of randomization to the date of disease progression determined by Lugano criteria by independent review committee (IRC) or death (whichever occurs first).
EOT CMR rate defined as the proportion of participants achieving CR per PET/CT Lugano 2014 criteria (protocol appendix B) at the EOT assessment: PET-CT, score 1, 2, or 3 with or without a residual mass on a 5-point scale (5PS) among all patients and separately in Cohorts A and B.
The number of participants experiencing Cytokine Release Syndrome (CRS) toxicity associated with Epcoritamab therapy will be reported, including Grades 2, 3 and 4. CRS-related toxicity will be assessed according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
The number of participants experiencing Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS)-related toxicity including Grades 2, 3 and 4. ICANS-related toxicity will be assessed according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
The number of participants experiencing neurologic toxicities associated with Epcoritamab therapy will be reported, including Grades 2, 3 and 4. Neurologic toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
The number of participants experiencing fluid accumulation associated with Loncastuximab therapy will be reported, including Grades 2, 3 and 4. Fluid accumulation toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
The number of participants experiencing hepatotoxicity (liver-related toxicity) associated with Loncastuximab therapy including Grades 2, 3 and 4 toxicity. Hepatotoxicity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
CR rate is defined as proportion of subjects with a CR based on the Lugano Criteria 2022 following 3 cycles of combination treatment.
CMR rate is defined as the proportion of participants who achieved CMR during study. CMR assessed by PET/CT is defined using Lugano criteria.
CMR rate is defined as the proportion of participants who achieved CMR during study. CMR assessed by PET/CT or CT is defined using Lugano criteria.
CMR will be assessed by PET-CT using the Deauville 5-point scale and Lugano 2014 criteria. Patients who die from any cause or relapse/progress prior to this time-point will be considered non-responders. Patients who don't have a PET-CT scan within the protocol defined window or withdraw from the trial prior to this time-point will be considered non outcome evaluable. Patients who undergo stem-cell transplant (SCT) within 24 weeks of randomisation, patients who fail to start treatment and patients whose ineligibility is deemed to impact upon response to treatment will be replaced and hence not included in the analysis of this outcome
The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on modified IWWM6 criteria.
uMRD CR as defined by negative leukemia cells to the 10\^6 after 12 cycles of consolidative therapy with epcoritamab measured by Adaptive's NGS MRD assay (ClonoSEQ) in patients who have attained a partial response or better with detectable disease after acalabrutinib or zanubrutinib +/- obinutuzumab treatment for a minimum of 12 cycles of therapy
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Efficacy will be determined by rate of uMRD at EOT for both Epcoritamab and BTKi discontinuation
Cytokine Release Syndrome events will be graded using American Society for Transplantation and Cellular Therapy (ASTCT), with a higher grade indicating higher severity.
ICANS events will be graded using ASTCT, with a higher grade indicating higher severity.
Ntox is defined as the percentage of participants who developed at least 1 Grade 3 or higher Ntox since the initiation of epcoritamab treatment.
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
AEs will be tabulated by type and grade using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and displayed in summary form. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
CRS severity will be graded using American Society for Transplantation and Cellular Therapy Cytokine Release Syndrome criteria. The CRS rate will be calculated together with 95% one-sided confidence intervals among evaluable patients.
The primary objective is to evaluate the feasibility and efficacy of prophylactic administration of siltuximab prior to infusion of the first dose of epcoritamab with the purpose of preventing all-grade CRS, as measured by incidence of all-grade cytokine release syndrome.
Will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) grading for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The dose limiting toxicity period will be the first 28 days after the first dose of epcoritamab.
Kaplan-Meier estimates will be provided. 95% confidence intervals will be generated.
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Maximum observed concentration.
AUC from time 0 to time of last measurable concentration within the dosing interval.
Best overall response (BOR) is defined as the percentage of participants in Cohort 1 Part 2 third line plus (3L) R/R DLBCL who achieved best overall response of complete response (CR) or partial response (PR) by Lugano 2014 criteria as assessed by independent review committee (IRC).
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
DLT events were defined as clinically significant adverse events (AEs) or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications as assessed per Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.
CRS and ICANS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria. CTLS will be graded according to Cairo-Bishop criteria.
R/R CLL participants will be assessed according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and the RS participants according to Lugano criteria. ORR based on the Lugano criteria is defined as the percentage of participants who achieve a response of PR or complete remission (CR), prior to initiation of subsequent therapy. The ORR based on the iwCLL criteria is defined as the percentage of participants who achieve a response of PR, CR with incomplete bone marrow recovery (CRi), or CR, prior to the initiation of subsequent therapy.
DLT events are defined as clinically significant adverse events (AEs) or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications as assessed per Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign. (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.
To determine the MTD and/or RP2D to be studied in the Expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.
CRS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
| Arm | Type | Description |
|---|---|---|
| Arm A: Epcoritamab Plus Lenalidomide (E-Len) | EXPERIMENTAL | Participants will receive E-Len for up to 12 cycles (each cycle is 28 days). |
| Arm B: Rituximab Plus Gemcitabine and Oxaliplatin (R-GemOx) | EXPERIMENTAL | Participants will receive R-GemOx for up to 4 cycles (each cycle is 28 days) |
| Arm C: Epcoritamab | EXPERIMENTAL | Participants will receive epcoritamab for up to 12 cycles (each cycle is 28 days). |
| Arm A1: Epcoritamab + Lenalidomide and Rituximab (R2) | EXPERIMENTAL | Participants will receive epcoritamab in combination with R2 (ER2), followed by epcoritamab during the 120 week treatment duration. |
| Arm A2: Epcoritamab + Lenalidomide and Rituximab (R2) | EXPERIMENTAL | Participants will receive epcoritamab in combination with R2 (ER2), during the 24 week treatment duration. |
| Arm B: Chemoimmunotherapy (CIT) Option A | EXPERIMENTAL | Participants will receive CIT Option A (obinutuzumab (G) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) \[G-CHOP\]/ rituximab (R)-CHOP during the 120 week treatment duration. |
| Arm B: Chemoimmunotherapy (CIT) Option B | EXPERIMENTAL | Participants will receive CIT Option B (G and bendamustine (Benda) \[G-Benda\]/R-Benda during the 120 week treatment duration. |
| Arm C: Lenalidomide and Rituximab (R2) | EXPERIMENTAL | Participants will receive lenalidomide and rituximab (R2) during the 120 week treatment duration. |
| Epcoritamab and R-CHOP | EXPERIMENTAL | Participants will receive subcutaneous epcoritamab combined with intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by epcoritamab in 21-day cycles. |
| R-CHOP and Rituximab | EXPERIMENTAL | Participants will receive intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by intravenous rituximab in 21-day cycles. |
| Epcoritamab Dose A in Combination With R2 | EXPERIMENTAL | Participants will receive epcoritamab Dose A in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days). |
| Epcoritamab Dose B in Combination With R2 | EXPERIMENTAL | Participants will receive epcoritamab Dose B in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days). Enrollment is closed for this arm. |
| Lenalidomide and Rituximab (R2) | ACTIVE_COMPARATOR | Participants will receive lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days). |
| Epcoritamab + Rituximab | EXPERIMENTAL | Participants will undergo study procedures as outlined: * PET/CT scans at baseline and after cycles 2, 5, and 9 of treatment. * Cycle 1: * Days -14, -7, 1, 8 of 6 week cycle: Predetermined dose of Rituximab. * Days 1, 8, 15, 22 of 6 week cycle: Predetermined dose of Epcoritamab. (Day 15 of Epcoritamab dosage will be administered in the hospital.) * Cycles 2 - 3: --Days 1, 8, 15, 22 of 4 week cycle: Predetermined dose of Epcoritamab. * Cycles 4 - 9: * Day 1 of 4 week cycle: Predetermined dose of Epcoritamab. * Day 15 of 4 week cycle: Predetermined dose of Epcoritamab. * Surveillance imaging (PT/CT scans) at months 13, 18, and 24 after initiation of treatment. * Follow up visits for up to 5 years. |
| Epcoritamab + Rituximab Expansion | EXPERIMENTAL | Participants will undergo study procedures as outlined: * PET/CT scans at baseline and after cycles 2, 5, and 9 of treatment. * Cycle 1: * Days -14, -7, 1, 8 of 6 week cycle: Predetermined dose of Rituximab. * Days 1, 8, 15, 22 of 6 week cycle: Predetermined dose of Epcoritamab. * Cycles 2 - 3: --Days 1, 8, 15, 22 of 4 week cycle: Predetermined dose of Epcoritamab. * Cycles 4 - 9: * Day 1 of 4 week cycle: Predetermined dose of Epcoritamab. * Surveillance imaging (PT/CT scans) at months 13, 18, and 24 after initiation of treatment. * Follow up visits for up to 5 years. |
| EPCOR in combination with LONCA Treatment Group | EXPERIMENTAL | Participants in the Epcoritamab (EPCOR) in combination with Loncastuximab (LONCA) treatment group will receive up to 4 cycles of combination EPCOR and LONCA therapy, and an additional 8 cycles of EPCOR therapy, for a total of twelve treatment cycles. Cycles 1 through 3 last 21 days each; cycles four through 12 last 28 days each. Protocol therapy will last approximately 12 months. Total participation duration is approximately 3 years. |
| GDP + Epcoritamab + AutoSCT or CAR T-cell therapy | EXPERIMENTAL | Cycles 1-3 (Cycle = 21 days) Epcoritamab will be administered by subcutaneous injection Days 1, 8, and 15. Epcoritamab Day 1: 0.16mg, Day 8: 0.8mg, Day 15: 48mg except Cycle 2-Epcoritamab will administered at 48mg on Days 1, 8 and 15 Gemcitabine will be administered by IV infusion on Days 1 and 8. Gemcitabine Days 1,8: 1,000mg/m\^2 Cisplatin will be administered by IV infusion on Day 1. Cisplatin Day 1: 75mg/m\^2 Dexamethasone will be given by mouth on Days 1-4. Dexamethasone Days 1-4: 40mg After completion of Cycle 3 Autologous stem cell transplant (AutoSCT) OR CAR T-cell therapy |
| GDP + Epcoritamab + Epcoritamab Maintenance | EXPERIMENTAL | Cycles 1-3 (Cycle = 21 days) Epcoritamab will be administered by subcutaneous injection Days 1, 8, and 15 of each Cycle. Epcoritamab Day 1: 0.16mg, Day 8: 0.8mg, Day 15: 48mg except Cycle 2-Epcoritabab will administered at 48mg on Days 1, 8 and 15 Gemcitabine will be administered by IV infusion on Days 1 and 8 of each Cycle. Gemcitabine Days 1,8: 1,000mg/m\^2 Cisplatin will be administered by IV infusion on Day 1 of each Cycle. Cisplatin Day 1: 75mg/m\^2 Dexamethasone will be given by mouth on Days 1-4 of Cycle 1 ONLY. Dexamethasone Days 1-4: 40mg Cycles 4-9 (Cycle =28 Days) Epcoritamab will be administered by subcutaneous injection on Days 1, 8, and 15 of Cycles 4-9. |
| Rituxan + Zanubrutinib + Epcoritamab for FL | EXPERIMENTAL | Enrolled participants will complete: * Baseline visit with imaging and bone marrow biopsy * Imaging on cycles 3, 6, 9 * Up to 1 year of treatment with study drugs * End of Treatment visit with imaging and bone marrow biopsy * Follow up visits every 6 months for up to 10 years |
| Rituxan + Zanubrutinib + Epcoritamab for MZL | EXPERIMENTAL | Enrolled participants will complete: * Baseline visit with imaging and bone marrow biopsy * Imaging on cycles 3, 6, 9 * Up to 1 year of treatment with study drugs * End of Treatment visit with imaging and bone marrow biopsy * Follow up visits every 6 months for up to 10 years |
| Round 1: Epcoritamab and lenalidomide | EXPERIMENTAL | Epcoritamab (weekly for cycles 1 and 2 and on day 1 of cycles 3-12 for up to 12 cycles) and lenalidomide (daily for days 1-21 of each cycle for up for 12 cycles), cycles will be 28 day cycles. |
| Round 2 | EXPERIMENTAL | Investigation agent 2 |
| Round 3 | EXPERIMENTAL | Investigation agent 3 |
| All rounds: Investigator Choice Therapy | ACTIVE_COMPARATOR | Choice of therapy to be selected by the Investigator for each patient prior to randomisation. The Investigator will choose between; RCHOP, RCVP, rituximab and bendamustine, rituximab and lenalidomide or bendamustine and obinutuzumab. |
| Epcoritamab Group | EXPERIMENTAL | Participants will receive up to 12 cycles of Epcoritamab therapy, each cycle lasting 28 days. Total participation is up to 3 years. |
| Safety Lead-In Epcoritamab | EXPERIMENTAL | Participants will be enrolled using a modified 3+3 dose-escalation design to establish the Recommended Phase 2 Dose of Epcoritamab and will complete study procedures as follows: * Baseline visit with CT scan and bone marrow biopsy. * Bone marrow biopsy before cycle 6. * Cycles 1 - 3: --Days 1, 8, 15, and 22 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * Cycles 4 - 9: --Days 1 and 15 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * Cycles 10 - 12: --Day 1 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * End of Treatment visit with CT scan and bone marrow biopsy. * Follow up visits: every 3 months for 2 years * Off study visit * If there are 0 out of 3 dose-limiting toxicities (DLTs), the study will proceed to phase II. If 1/3 participants experience a DLT, up to 3 additional participants will be treated at the same dose level. If more than 1/6 total participants experience a DLT, then the study will not proceed to phase 2. |
| Phase II Epcoritamab | EXPERIMENTAL | Participants will be enrolled and will complete study procedures as follows: * Baseline visit with CT scan and bone marrow biopsy. * Bone marrow biopsy before cycle 6. * Cycles 1 - 3: --Days 1, 8, 15, and 22 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * Cycles 4 - 9: --Days 1 and 15 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * Cycles 10 - 12: --Day 1 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * End of Treatment visit with CT scan and bone marrow biopsy. * Follow up visits: every 3 months for 2 years * Off study visit |
| Epcoritamab + SOC | EXPERIMENTAL | Epcoritamab is the investigational product under study in combination with SOC drugs in this protocol. During C1, epcoritamab will be initiated using step-up dosing (SUD) C1D1 .16mg, C1D8 .8mg, C1D15 3 mg, C1D22 24 mg vs 48 mg (full dose) during safety lead in to determine the RP2D. On Cycles 2-3 the RP2D (24mg vs 48 mg) will be administered on Days 1, 8, 15, 22. Then Cycles 4-9 RP2D will be administered on Days 1 \& 15. Then Cycle 10-12 RP2D on Day 1 of each cycle. Epcoritamab is administered subcutaneously. The SOC BTKi are oral medications administered daily during the trial period. |
| EPCORI Arm | EXPERIMENTAL | - |
| OBS Arm | EXPERIMENTAL | - |
| Epcoritamab | EXPERIMENTAL | Given IV |
| Main Cohort: Epcoritamab Diffuse Large B-Cell Lymphoma (DLBCL) | EXPERIMENTAL | Participants with relapsed or refractory (R/R) DLBCL will receive subcutaneous (SC) epcoritamab in 28 day cycles. |
| Main Cohort: Epcoritamab Classic Follicular Lymphoma (cFL) | EXPERIMENTAL | Participants with R/R cFL will receive SC epcoritamab in 28 day cycles. |
| Diversity Enriched Cohort: Epcoritamab DLBCL | EXPERIMENTAL | Participants with R/R DLBCL will receive SC epcoritamab in 28 day cycles. |
| Diversity Enriched Cohort: Epcoritamab cFL | EXPERIMENTAL | Participants with R/R cFL will receive SC epcoritamab in 28 day cycles. |
| Arm 1: Dose Escalation | EXPERIMENTAL | Participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) will receive escalating doses of epcoritamab in combination with lenalidomide in 28 day cycles. |
| Arm 2: Dose Escalation | EXPERIMENTAL | Participants with R/R DLBCL will receive escalating doses of epcoritamab in combination with ibrutinib and lenalidomide in 28 day cycles. |
| Arm 3: Dose Escalation | EXPERIMENTAL | Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles. |
| Arm 4: Dose Escalation | EXPERIMENTAL | Participants with R/R DLBCL will receive escalating doses of epcoritamab in combination with CC-99282 in 28 day cycles. |
| Arm 5: Dose Escalation | EXPERIMENTAL | Participants with R/R follicular lymphoma (FL) will receive escalating doses of epcoritamab in combination with CC-99282 in 28 day cycles. |
| Arm 6A: Dose Escalation | EXPERIMENTAL | Participants with R/R mantle cell lymphoma (MCL) will receive escalating doses of epcoritamab in combination with ibrutinib in 28 day cycles. |
| Arm 1: Dose Expansion | EXPERIMENTAL | Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with lenalidomide in 28 day cycles. |
| Arm 2: Dose Expansion | EXPERIMENTAL | Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles. |
| Arm 3: Dose Expansion | EXPERIMENTAL | Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles. |
| Arm 3B: Dose Expansion | EXPERIMENTAL | Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP), in 21 day cycles,until unacceptable toxicity, withdrawal of consent, or completion of treatment. |
| Arm 4: Dose Expansion | EXPERIMENTAL | Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with CC-99282 in 28 day cycles. |
| Arm 5: Dose Expansion | EXPERIMENTAL | Participants with R/R FL will receive the recommended dose of epcoritamab in combination with CC-99282 in 28 day cycles. |
| Arm 6: Dose Expansion | EXPERIMENTAL | Participants with R/R MCL will receive the recommended dose of epcoritamab in combination with ibrutinib in 28 day cycles. |
| Treatment (epcoritamab, ibrutinib) | EXPERIMENTAL | Patients receive ibrutinib PO QD on days -7 to 28 of cycle 1 and on days 1 to 28 of remaining cycles, as well as epcoritamab SC on days 1, 8, 15 and 22 of cycles 1-3, days 1 and 15 of cycles 4-9, and on day 1 of remaining cycles. Treatment repeats every 28 days for up to 6 cycles of ibrutinib and up to 12 cycles of epcoritamab in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT and PET/CT throughout the study. Patients may also undergo bone marrow aspiration and biopsy on study. |
| Prophylactic siltuximab + epcoritamab | EXPERIMENTAL | Siltuximab Administration: • Participants will receive a single dose of prophylactic siltuximab, 11mg/kg, started 1 hour prior (+/- 60 minutes) to the infusion of epcoritamab. There is no planned dose escalation of siltuximab and epcoritamab dosing will be done following the standard planned ramp-up over the course of the first 3 weeks Epcoritamab Infusion: • The treatment regimen of epcoritamab is done in 28-day cycles. Epcoritamab is to be administered by subcutaneous injection. Participants can be treated for up to 24 cycles. Participants who achieve complete remission at the time of their disease response assessment after 12 cycles may be considered for early discontinuation of treatment. |
| Treatment (epcoritamab) | EXPERIMENTAL | Patients receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 4-9, and day 1 of each subsequent cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR may continue to receive epcoritamab if disease progression occurs within 6 months. Patients with PR or SD continue to receive epcoritamab in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and blood sample collection throughout the study and may undergo biopsy during screening. |
| Treatment (epcoritamab, pola-r-mini-CHP) | EXPERIMENTAL | See Detailed Description |
| Cohort 1 Part 1: Epcoritamab Monotherapy | EXPERIMENTAL | Participants will receive subcutaneous (SC) epcoritamab in 28 day cycles. |
| Cohort 1 Part 2: Epcoritamab Expansion | EXPERIMENTAL | Participants will receive SC epcoritamab in 28 day cycles. |
| Cohort 2: Epcoritamab + RCHOP | EXPERIMENTAL | Participants will receive SC epcoritamab in combination with \[intravenously (IV) infused rituximab, IV injected cyclophosphamide, IV infused doxorubicin, IV infused vincristine, and oral prednisone (R-CHOP)\] in 21 day cycles followed by 28 day cycles. |
| Cohort 3: Epcoritamab + R2 | EXPERIMENTAL | Participants will receive SC epcoritamab in combination with \[intravenously (IV) infused rituximab, and oral lenalidomide (R2)\] in 28 day cycles. |
| Epcoritamab in R/R CLL/SLL | EXPERIMENTAL | In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase. |
| Epcoritamab in RS | EXPERIMENTAL | Only in expansion phase. |
| Epcoritamab + Venetoclax in R/R CLL/SLL | EXPERIMENTAL | In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase. |
| Epcoritamab + Lenalidomide in RS | EXPERIMENTAL | Only in expansion phase. |
| Epcoritamab + R-CHOP in RS | EXPERIMENTAL | Only in expansion phase. |
| Epcoritamab + Pirtobrutinib in R/R CLL, TN HR CLL (Non-US Participants Only) and SLL | EXPERIMENTAL | Safety run-in and expansion phases. |
| Fixed Duration Epcoritamab in R/R CLL/SLL | EXPERIMENTAL | Only in expansion phase. |
| Arm 1 - Epcoritamab + R-CHOP | EXPERIMENTAL | In participants with previously untreated DLBCL. |
| Arm 2 - Epcoritamab + R2 | EXPERIMENTAL | In participants with R/R FL. |
| Arm 3 - Epcoritamab + BR | EXPERIMENTAL | In participants with previously untreated FL. |
| Arm 4 - Epcoritamab + R-DHAX/C | EXPERIMENTAL | In participants with R/R DLBCL eligible for ASCT. |
| Arm 5 - Epcoritamab + GemOx | EXPERIMENTAL | In participants with R/R DLBCL ineligible ASCT. |
| Arm 6 - Epcoritamab + R2 | EXPERIMENTAL | In participants with previously untreated FL. |
| Arm 7 - Epcoritamab maintenance | EXPERIMENTAL | In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L. |
| Arm 8 - Epcoritamab + R mini-CHOP | EXPERIMENTAL | In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline. |
| Arm 9 - Epcoritamab + Lenalidomide | EXPERIMENTAL | In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy. |
| Arm 10 - Epcoritamab + R-ICE | EXPERIMENTAL | In participants with R/R DLBCL eligible for ASCT. |
| Name | Type | Description |
|---|---|---|
| Epcoritamab | BIOLOGICAL | Following mandatory pre-medication, participants will be administered epcoritamab as a subcutaneous injection. |
| Investigator's Choice Chemotherapy | DRUG | Following mandatory pre-medication, participants will be administered intravenously either BR or R-GemOx. |
| Rituximab | DRUG | Intravenous (IV) Infusion |
| Lenalidomide | DRUG | Oral Capsule |
| Oxaliplatin | DRUG | IV Infusion |
| Gemcitabine | DRUG | IV Infusion |
| Prednisone | DRUG | Oral Tablet |
| Doxorubicin | DRUG | IV Injection |
| Vincristine | DRUG | IV Injection |
| Cyclophosphamide | DRUG | IV Injection |
| Obinutuzumab | DRUG | IV Infusion |
| Bendamustine | DRUG | IV Infusion |
| Loncastuximab Tesirine | DRUG | Loncastuximab will be administered intravenously (IV) at the following dose level and schedule over a total of four cycles: * Cycles 1 and 2 Day 1: 120 mcg/kg * Cycles 3 and 4 Day 1: 75 mcg/kg * Cycle 4 Day 22: 75 mcg/kg |
| AutoSCT OR CAR T-cell Therapy | PROCEDURE | Autologous stem cell transplant (AutoSCT) or CAR T-cell therapy will be performed after Cycle 3 of receiving epcoritamab and GDP |
| GDP | DRUG | Gemcitabine Cisplatin Dexamethasone |
| Zanubrutinib | DRUG | Bruton tyrosine kinase inhibitor, 80 mg immediate-release capsule, taken orally per protocol. |
| Investigation agent 2 | DRUG | The drug used in round 2 is yet to be confirmed, round 2 is estimated to open in Q4 2025 and the record will be updated when the drug has been confirmed |
| Investigation agent 3 | DRUG | The drug used in round 3 is yet to be confirmed, round 3 is estimated to open in Q3 2027 and the record will be updated when the drug has been confirmed |
| Observation | OTHER | Participant will be closely monitored until the disease gets worse and requires treatment, as determined by your treating doctor or at your request. |
| Ibrutinib | DRUG | Oral; Capsule |
| Doxorubicin Hydrochloride [HCl] | DRUG | IV; Injection |
| Polatuzumab Vedotin | DRUG | IV; Injection |
| CC-99282 | DRUG | Oral; Capsule |
| Epcoritamab (monotherapy) | BIOLOGICAL | Epcoritamab will be administered subcutaneously in cycles of 4 weeks (i.e. 28 days) |
| Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone | DRUG | 21-day cycles |
| Gemcitabine and oxaliplatin | DRUG | 28-day cycles |
| Epcoritamab (maintenance) | BIOLOGICAL | 28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13 |
| Rituximab and lenalidomide | DRUG | 28-day cycles. |
| Biospecimen Collection | PROCEDURE | Undergo blood sample collection |
| Bone Marrow Aspiration | PROCEDURE | Undergo bone marrow aspiration and biopsy |
| Bone Marrow Biopsy | PROCEDURE | Undergo bone marrow aspiration and biopsy |
| Computed Tomography | PROCEDURE | Undergo CT and PET/CT |
| Positron Emission Tomography | PROCEDURE | Undergo PET/CT |
| Siltuximab | DRUG | Single dose of prophylactic siltuximab, 11mg/kg, started 1 hour prior (+/- 60 minutes) to the infusion of epcoritamab. |
| Biopsy | PROCEDURE | Undergo biopsy |
| Magnetic Resonance Imaging | PROCEDURE | Undergo brain MRI |
| rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone | DRUG | R-CHOP will be administered intravenously (prednisone may be administered orally) in cycles of 21 days. |
| Venetoclax | DRUG | Venetoclax tablets will be administered orally once daily during the 5-week ramp up period in cycles of 28 or 35 days each. |
| Pirtobrutinib | DRUG | Pirtobrutinib tablets will be administered in cycles of 28 days. |
| rituximab and bendamustine | DRUG | 6 cycles (28-day cycles) |
| rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin | DRUG | 3 cycles (21-day cycles) |
| rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone | DRUG | 6 cycles (21-day cycles) |
| rituximab, ifosfamide, carboplatin, and etoposide phosphate | DRUG | 3 cycles (21-day cycles) |
Inclusion Criteria: * Eastern Cooperative Oncology Group Performance status score of 0 to 2. * Histologically confirmed CD20+ Diffuse Large B-Cell Lymphoma (DLBCL) and documented in the most recent and representative pathology report, inclusive of the following according to the World Health Organiz...
Epcoritamab is an investigational monoclonal antibody being developed by Genmab A/S for B-cell malignancies. It is being studied in B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia (CLL), CLL/SLL, diffuse large B-cell lymphoma (DLBCL), and diffuse large B-cell lymphoma post-transplant lymphoproliferative disorder. It is in clinical development and is not described as approved.
Epcoritamab targets MS4A1 (CD20) on B cells and the CD3 subunits CD3E, CD3G, and CD3D on T cells. By binding both a B-cell surface antigen and the T-cell receptor complex, it is designed to redirect T cells toward B-cell lymphoma cells. It is classified as a binding agent.
Epcoritamab is developed by Genmab A/S, which trades under the ticker GMAB. Genmab is the sponsor associated with the epcoritamab clinical program across its lymphoma and leukemia studies.
Epcoritamab is in clinical development, with studies spanning Phase 1 through Phase 3. It is investigational and is not described as FDA approved. The program includes nine trials in total, of which eight are active and none are completed, with a combined planned enrollment of 2,771 participants.
Epcoritamab trials include NCT07819214, a Phase 2 study of epcoritamab as consolidation therapy for high-risk CLL patients on BTK inhibitors, and NCT07783594, a randomized Phase 2 study comparing epcoritamab with watch and wait in previously untreated low tumor burden follicular lymphoma. NCT07714421 is a Phase 1 study combining epcoritamab with Pola-R-mini-CHP in elderly or unfit DLBCL patients, and NCT07226752 is a Phase 3 sub-study in relapsed or refractory DLBCL in China.
Yes. Epcoritamab is also referred to as epcoritamab (monotherapy), which describes its use as a single agent rather than in combination with other therapies. Both names refer to the same monoclonal antibody developed by Genmab A/S.