On December 7, 2020 Incyte (Nasdaq:INCY) and MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; NASDAQ:MOR) reported that preliminary data from firstMIND, the ongoing Phase 1b, open-label, randomized study on the safety and efficacy of tafasitamab or tafasitamab plus lenalidomide in addition to R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were presented today during the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper) (Press release, Incyte, DEC 7, 2020, View Source [SID1234572327]). Additionally, a long-term subgroup analysis of the L-MIND study investigating tafasitamab combined with lenalidomide in patients with relapsed or refractory DLBCL was also presented at ASH (Free ASH Whitepaper).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The preliminary results of firstMIND indicate that tafasitamab plus lenalidomide in addition to R-CHOP shows an acceptable tolerability profile. Toxicities appear to be similar to what is expected with R-CHOP alone or in combination with lenalidomide. Serious or severe neutropenia and thrombocytopenia events (grade 3 or higher) were more frequent in the tafasitamab plus lenalidomide arm. The incidence of febrile neutropenia was comparable between both arms and the average relative dose intensity of R-CHOP was maintained in both arms. Interim response assessments after three cycles were available for 45 patients. In both arms combined, 41/45 (91.1%) of patients had an objective response as per Lugano 20141.

The preliminary data from this ongoing study in first-line DLBCL warrant further investigation. To that end, MorphoSys and Incyte plan to initiate frontMIND, a Phase 3 trial evaluating tafasitamab plus lenalidomide in combination with R-CHOP compared to R-CHOP alone as first-line treatment for patients with newly diagnosed DLBCL.

"The initial results of the firstMIND study, shared today at ASH (Free ASH Whitepaper), as well as the long-term analyses from L-MIND, underscore the potential of tafasitamab as a combination therapeutic for patients with DLBCL, where there remains a significant unmet need. Along with our partners at MorphoSys, we are pleased to be moving forward with the initiation of a Phase 3 study in 2021," said Steven Stein, M.D., Chief Medical Officer at Incyte.

"The preliminary firstMIND study results mark another important step as we explore the potential of tafasitamab as a backbone therapy," said Dr. Malte Peters, Chief Research and Development Officer at MorphoSys. "Given the data available to date, including data from the L-MIND study, we believe that the mechanism of action, efficacy and safety profile of tafasitamab have the potential to make it a preferred combination partner as we seek to transform the standard of care in DLBCL. We are committed to developing innovative therapies to battle this aggressive disease for the benefit of patients with DLBCL, and look forward to beginning the planned frontMIND in the first half of 2021."

In addition to the firstMIND data presented today, the long-term L-MIND analyses showed that treatment with tafasitamab plus lenalidomide resulted in durable responses after ≥2 years of follow-up. At the time of analysis, patients with complete responses (CR) continued to experience durable treatment responses, including long duration of response (DoR) and overall survival (OS). The data also showed that tafasitamab plus lenalidomide taken for 12 cycles, followed by tafasitamab until progression, did not result in any unexpected safety signals2.

In July 2020, the FDA approved Monjuvi (tafasitamab-cxix), a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody, in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)3.

The FDA decision represented the first approval of a second-line treatment for adult patients with DLBCL who progressed during or after first-line therapy.

About Diffuse Large B-cell Lymphoma (DLBCL)

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide4, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter5. In the United States each year, approximately 10,000 patients are diagnosed with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant (ASCT)6,7,8.

About firstMIND

The firstMIND (NCT04134936) trial is a Phase 1b, randomized study of tafasitamab + R-CHOP (Arm A) or tafasitamab + lenalidomide + R-CHOP (Arm B) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The study includes a safety run-in phase and a main phase. In the safety run-in phase, 24 patients were enrolled. The primary objective is to assess safety; secondary objectives include objective response rate, PET negative complete response (PET-CR) rate at end of treatment, progression-free survival, event-free survival, long-term safety, pharmacokinetics and immunogenicity of tafasitamab.

About Tafasitamab

Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Monjuvi(tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In January 2020, MorphoSys and Incyte entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. Monjuvi is being co-commercialized by Incyte and MorphoSys in the United States. Incyte has exclusive commercialization rights outside the United States.

A marketing authorization application (MAA) seeking the approval of tafasitamab in combination with lenalidomide in the EU has been validated by the European Medicines Agency (EMA) and is currently under review for the treatment of adult patients with relapsed or refractory DLBCL, including DLBCL arising from low grade lymphoma, who are not candidates for ASCT.

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in a number of ongoing combination trials.

Monjuvi is a registered trademark of MorphoSys AG.

XmAb is a registered trademark of Xencor, Inc.

Important Safety Information

What are the possible side effects of MONJUVI?

MONJUVI may cause serious side effects, including:

Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get chills, flushing, headache, or shortness of breath during an infusion of MONJUVI.
Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or any bruising or bleeding.
Infections. Serious infections, including infections that can cause death, have happened in people during treatments with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or develop any signs and symptoms of an infection.
The most common side effects of MONJUVI include:

Feeling tired or weak
Diarrhea
Cough
Fever
Swelling of lower legs or hands
Respiratory tract infection
Decreased appetite
These are not all the possible side effects of MONJUVI.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before you receive MONJUVI, tell your healthcare provider about all your medical conditions, including if you:

Have an active infection or have had one recently.
Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.
You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.
Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.
Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.
You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

On December 7, 2020 Incyte (Nasdaq:INCY) reported data from three ongoing Phase 2 studies evaluating parsaclisib, a potent, highly selective, next-generation oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), for the treatment of patients with relapsed or refractory follicular (CITADEL-203), marginal zone (CITADEL-204) and mantle cell (CITADEL-205) lymphomas (Press release, Incyte, DEC 7, 2020, View Source [SID1234572326]). These data were accepted for presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2020), held virtually from December 5–8, 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The primary endpoint for the CITADEL-203, -204 and -205 studies is objective response rate (ORR); duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and tolerability are among the secondary endpoints. All radiology-based endpoints are based on independent review committee (IRC) assessment.

Eligible patients received parsaclisib 20 mg once daily for eight weeks followed by either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg once daily (daily-dosing group [DG]). Subsequently, daily dosing was selected as the preferred regimen and patients initially enrolled in the WG were allowed to switch to DG. Data are presented for the DG and all patients.

Key results from the CITADEL studies include:

ORR (95% CI), %

mDOR (95% CI),

months

mPFS (95% CI),

months

mOS (95% CI),

months

CITADEL-203: R/R Follicular Lymphoma

DG (N=95)

75 (65-83)

14.7 (12.0-17.5)

15.8 (13.8-19.1)

–

All (N=118)

73 (64-81)

15.9 (12.0-NE)

15.8 (13.2-19.3)

–

CITADEL-204: R/R Marginal Zone Lymphoma

DG (N=72)

56.9 (44.7-68.6)

NR (8.1-NE)

NR (11.0-NE)

–

All (N=100)

57.0 (46.7-66.9)

12.0 (9.3-NE)

19.4 (13.7-NE)

–

CITADEL-205: R/R Mantle Cell Lymphoma (BTK Inhibitor Treatment Naive)

DG (N=77)

71 (60-81)

9.0 (6.7-14.7)

11.1 (8.3-NE)

NR (NE-NE)

All (N=108)

70 (61-79)

14.7 (7.7-NE)

11.1 (8.3-19.2)

NR (NE-NE)

CITADEL-205: R/R Mantle Cell Lymphoma (Previously Treated with Ibrutinib)

DG (N=41)

29 (16-46)

3.7 (1.9-NE)

3.7 (1.8-4.1)

11.2 (7.9-NE)

All (N=53)

25 (14-38)

3.7 (1.9-NE)

3.7 (1.8-3.9)

11.2 (7.9-17.1)

R/R: relapsed or refractory; ORR: objective response rate; mDOR: median duration of response (reported for responders); mPFS: median progression-free survival; mOS: median overall survival; DG: daily dosing group; BTK: Bruton’s tyrosine kinase.

Parsaclisib was generally well tolerated in all studies with a manageable safety profile.

"Data from the CITADEL studies presented at ASH (Free ASH Whitepaper) 2020 are very promising and they highlight the potential of parsaclisib to become a meaningful treatment for patients with relapsed or refractory follicular, marginal zone or mantle cell lymphomas," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "We look forward to continuing our work as we seek to bring this medicine to patients."

Presentations are available on the ASH (Free ASH Whitepaper) website at View Source; #338 (Oral presentation, CITADEL-204), #2935 (Poster, CITADEL-203), #1121 (Poster, CITADEL-205), #2044 (Poster, CITADEL-205).

About Follicular, Marginal Zone and Mantle Cell Lymphomas

Non-Hodgkin lymphoma (NHL) is a type of cancer that starts in the lymphocytes, a type of white blood cell. Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) are forms of B-Cell NHLs. FL and MZL are indolent or slow growing lymphomas; MCL is an aggressive or rapidly developing form. There is an unmet medical need for treatment options for patients who are relapsed or refractory to initial therapies.

About CITADEL

The CITADEL (Clinical Investigation of TArgeted PI3K-DELta Inhibition in Lymphomas) clinical trial program is evaluating parsaclisib in several ongoing studies as a treatment for adult patients with lymphomas, including:

CITADEL-203 (NCT03126019) is evaluating patients with relapsed or refractory follicular lymphoma (FL) Grade 1, 2 or 3a who received at least two prior systemic therapies, had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, and were ineligible for hematopoietic stem cell transplantation (HSCT).
CITADEL-204 (NCT03144674) is evaluating patients with relapsed or refractory marginal zone lymphoma (MZL) who received at least one prior systemic therapy and were Bruton’s tyrosine kinase (BTK) inhibitor treatment naive. Patients with prior ibrutinib treatment were initially allowed to enroll; however, the cohort was terminated due to slow enrollment. Eligible patients had radiologically measurable lymphadenopathy or extranodal lymphoid malignancy (or histologically confirmed bone marrow infiltration in cases of splenic MZL), and an ECOG PS ≤2.
CITADEL-205 ( NCT03235544 ) is evaluating patients with relapsed or refractory mantle cell lymphoma (MCL), who received one to three prior systemic therapies and were either naive to or were previously treated with a BTK inhibitor. Eligible patients had an ECOG PS ≤2, and radiologically measurable lymphadenopathy or extranodal lymphoid malignancy.
Patients eligible for each trial were allocated to receive parsaclisib 20 mg once daily for eight weeks followed by either 20 mg once weekly (weekly-dosing group [WG]) or 2.5 mg once daily (daily-dosing group [DG]). Subsequently, daily dosing was selected as the preferred regimen and the WG patients were allowed to switch to DG. Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was required.

About Parsaclisib

Parsaclisib is a potent, highly selective, next-generation investigational novel oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ). It is currently under evaluation as a monotherapy in several ongoing Phase 2 trials as a treatment for non-Hodgkin lymphomas (follicular, marginal zone and mantle cell); and autoimmune hemolytic anemia. Pivotal trials of parsaclisib in combination with ruxolitinib for the treatment of patients with myelofibrosis are underway; and there are plans to initiate a trial to evaluate parsaclisib in combination with tafasitamab for B-cell malignancies.

In December 2018, Innovent and Incyte entered into a strategic collaboration for three clinical-stage product candidates, including parsaclisib. Under the terms of the agreement, Innovent has received the rights to develop and commercialize parsaclisib and two other assets in Mainland China, Hong Kong, Macau and Taiwan.

Conference Call Information

Incyte will host an investor conference call and webcast at 10:00 a.m. ET (7:00 a.m. PT) today, December 7, 2020—the call and webcast can be accessed via the Events and Presentations tab of the Investor section of Incyte.com and it will be available for replay for 90 days.

On December 7, 2020 Sierra Oncology, Inc. (SRRA), a late-stage biopharmaceutical company on a quest to deliver targeted therapies that treat rare forms of cancer, reported an updated efficacy analyses of momelotinib in myelofibrosis patients with thrombocytopenia (Press release, Sierra Oncology, DEC 7, 2020, View Source [SID1234572324]). The data were presented in a poster presentation at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting by Jean-Jacques Kiladjian, MD, PhD, Consultant Hematologist, Head, Clinical Investigation Center, Saint Louis Hospital, Paris, France.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This retrospective analysis of the two Phase 3 SIMPLIFY studies demonstrate that the relative benefit-risk profile of momelotinib and ruxolitinib is influenced by baseline platelet count. What we show in this analysis is that momelotinib’s safety and activity profile do not appear to be affected by baseline platelet count, while in contrast, activity with ruxolitinib declined in patients with lower baseline platelet counts," said Dr. Kiladjian. "These updated data analyses complement previous findings that demonstrate the ability to initiate and maintain near-maximal momelotinib dose intensity regardless of baseline platelet count, suggesting that this durable dosing contributes to its efficacy profile."

"These exciting data provide a novel insight into a patient population where momelotinib’s unique receptor inhibition profile—JAK1, JAK2 & ACVR1—may be particularly relevant. The observation of preserved activity in patients with reduced platelet counts is provocative and potentially differentiating. The wealth of information contained in the SIMPLIFY studies will enable further analyses and potentially identify additional populations of interest to be presented at future scientific meetings," said Stephen Dilly, MBBS, PhD, Chief Executive Officer at Sierra Oncology. "We now look forward to completing enrollment in the pivotal Phase 3 MOMENTUM study and subsequent topline data to support our plan to file for regulatory approval of momelotinib for the treatment of myelofibrosis."

Momelotinib’s Spleen, Symptom and Anemia Efficacy is Maintained in Intermediate/High Risk Myelofibrosis Patients with Thrombocytopenia (Abstract #3086)

Dr. Kiladjian presented comparative efficacy data for momelotinib and ruxolitinib in patients with low platelets from the SIMPLIFY-1 (S1) and SIMPLIFY-2 (S2) Phase 3 studies. Results from the updated analyses include:

In S1 (JAKi-naïve), patients whose baseline platelet counts were:
<150 x 109/L, momelotinib achieved substantially higher TI (62% vs. 42%) and splenic response rates (23% vs. 4%) and a similar symptomatic response (28% vs. 33%) relative to ruxolitinib
150-300 x 109/L, generally similar splenic (35% vs. 32%) and symptom response rates (33% vs. 41%) and a higher TI response rate (72% vs. 54%) were achieved with momelotinib relative to ruxolitinib
>300 x 109/L, ruxolitinib achieved higher splenic (44% vs. 19%) and symptom response rates (46% vs. 23%) at week 24 than with momelotinib; the Week 24 TI rate remained higher with momelotinib (63% vs. 51%)
In S2 (JAKi-exposed patients):
Momelotinib’s response rates for the 3 response parameters remain very consistent with overall ITT response rates in patients whose baseline platelets were <150 x 109/L
Momelotinib’s symptomatic and anemia benefit were also preserved in patients whose baseline platelet counts were <50 and >50-100 x 109/L
In both S1 and S2, rates of TEAEs on momelotinib were generally similar between the overall safety population and subjects with baseline platelets <150 x 109/L
Patients were randomized 1:1 (S1) and 2:1 (S2) to receive momelotinib (200 mg QD) versus ruxolitinib (20 mg BID) or best available therapy (88.5% RUX/RUX+) for 24 weeks followed by extended momelotinib treatment. A baseline platelet limit of >50 x 109/L was required in S1 while there was not lower platelet limit for S2. Both trials had primary endpoints of Splenic Response Rate and secondary endpoints of Total Symptom Score and Transfusion Independence Rate.

About Momelotinib

Momelotinib is a selective and orally bioavailable JAK1, JAK2 and ACVR1 inhibitor currently under investigation for the treatment of myelofibrosis. Myelofibrosis results from dysregulated JAK-STAT signaling and is characterized by constitutional symptoms, splenomegaly (enlarged spleen) and progressive anemia.

Momelotinib is currently under investigation in the MOMENTUM clinical trial, a global, randomized, double-blind Phase 3 study for symptomatic and anemic myelofibrosis patients. Top-line data are anticipated in H1 2022. The U.S. Food & Drug Administration has granted Fast Track designation for momelotinib.

On December 7, 2020 Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (NYSE: LLY), reported clinical data from the LOXO-305 global Phase 1/2 BRUIN clinical trial in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) (Press release, Eli Lilly, DEC 7, 2020, View Source [SID1234572323]). LOXO-305 is an investigational, highly selective, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor. These data are being presented in an oral presentation at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (abstract 542).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The data presented at ASH (Free ASH Whitepaper) reveal an incredibly encouraging and consistent safety and efficacy profile for LOXO-305 in heavily pre-treated CLL and SLL patients, regardless of previous therapies, reasons for discontinuations of those therapies, or presence of resistance mutations", said Anthony Mato, M.D., director of the CLL Program at Memorial Sloan Kettering Cancer Center and the presenting author. "We are increasingly in need of new therapies for patients that have been previously treated with a covalent BTK inhibitor, and LOXO-305 may allow us to continue treating patients in the same biologic class before attempting more complicated therapeutic approaches."

"The LOXO-305 data continue to surpass our expectations, and we are very excited for what these data could mean for patients with CLL and SLL", said David Hyman, M.D., chief medical officer of Loxo Oncology at Lilly. "These emerging data further substantiate our thesis that the drug’s reversible binding mode, high selectivity, and robust pharmacology offer a differentiated treatment option across B-cell leukemias and lymphomas. We are eager to initiate a Phase 3 program in 2021."

Key Data Presented at ASH (Free ASH Whitepaper)

As of September 27, 2020, 323 patients were enrolled in the study, including 170 with CLL/SLL, 61 with mantle cell lymphoma (MCL), 26 with Waldenström’s macroglobulinemia, and 66 with other B-cell lymphomas. The CLL/SLL patients had received a median of three prior lines of therapy with 86% receiving a prior BTK inhibitor, 90% an anti-CD20 antibody, 82% chemotherapy, 34% venetoclax, 21% a PI3K inhibitor, 6% CAR-T therapy and 2% an allogeneic transplant.

Pharmacokinetic analyses during the dose escalation demonstrated consistent dose-proportional exposures with low inter-patient variability across the entire dosing range of 25mg to 300mg daily. Doses of 100mg QD and greater exceeded BTK IC90 target coverage for the entirety of the dosing interval. Responses were observed starting at the first dose level.

The efficacy data presented at ASH (Free ASH Whitepaper) are based on investigator response assessments. Patients were considered efficacy-evaluable if they had at least one post-baseline response assessment or if they discontinued treatment prior to their first post-baseline response assessment. In 139 efficacy-evaluable patients with CLL/SLL treated across all dose levels, 88 responded including 69 partial responses (PR), 19 partial responses with ongoing lymphocytosis (PR-L), 45 stable disease (SD), one progressive disease (PD), five discontinued prior to their first response assessment and were considered non-evaluable (NE), resulting in an overall response rate (ORR) of 63% (95% CI: 55-71). The ORR was consistent in various subsets of patients, including:

In the 121 efficacy-evaluable BTK-pretreated patients, the ORR was 62% (95% CI: 53-71), rising to 84% (21/25) for those followed 10 months or more. This deepening of response over time is consistent with other BTK inhibitors and suggests the overall efficacy profile of LOXO-305 will continue to strengthen with additional follow-up.
The ORR was similar in patients who previously discontinued a covalent BTK inhibitor for progression (67% [53/79]) versus toxicity or another reason (52% [22/42]).
The ORR was also similar in those with a BTK C481 mutation (71% [17/24]) and those without (66% [43/65]).
In patients who previously received prior chemoimmunotherapy, a covalent BTK inhibitor and a BCL-2 inhibitor the ORR was 69% (27/39).
In patients who previously received all five classes of available CLL/SLL therapy including prior chemoimmunotherapy, a covalent BTK inhibitor, a BCL-2 inhibitor, and a PI3K inhibitor the ORR was 58% (7/12).
In the 28 patients with a 17p deletion, TP53 mutation, or both, the ORR was 79% (22/28).
As of the data cut-off, 88% of all CLL/SLL patients remain on LOXO-305. Median follow-up for efficacy-evaluable CLL/SLL patients was six months. Of the 88 responding CLL/SLL patients, all except five remain on therapy (four progressed and one achieved a PR and electively discontinued to pursue a transplant). The longest-followed responding patient continues on treatment at 17.8 months.

Safety data were presented for the entire enrolled BRUIN population. Across all 323 patients enrolled in the study, the most commonly reported adverse events, regardless of attribution, were fatigue (20%), diarrhea (17%), and contusion (13%). In addition, rates of two adverse events commonly associated with BTK inhibitors, atrial arrythmias and hemorrhage, were low, experienced by two patients and one patient respectively, and considered by investigators as unrelated to LOXO-305. Dose interruptions, reductions and permanent discontinuations for drug-related adverse events were observed in 8%, 2.2%, and 1.5% of patients, respectively. No dose limiting toxicities were reported and a maximum tolerated dose (MTD) was not reached.

LOXO-305 Development Program Update

In addition to the previously announced Phase 3 MCL trial, Loxo Oncology at Lilly is preparing to initiate two global, randomized, Phase 3 clinical trials in BTK pre-treated patients with CLL/SLL. The trials will explore LOXO-305, alone and in combination as follows:

BRUIN CLL-321: CLL/SLL patients who progressed or were intolerant to covalent BTK inhibitor treatment will be randomized to receive continuous LOXO-305 therapy or investigator’s choice of either Idelalisib plus Rituximab or Bendamustine plus Rituximab. This trial is expected to start in the first quarter of 2021.
BRUIN CLL-322: CLL/SLL patients who progressed or were intolerant to covalent BTK inhibitor treatment will be randomized to receive a time-limited combination of either LOXO-305 plus venetoclax and Rituximab or venetoclax and Rituximab. This trial is expected to start in the second quarter of 2021.
In addition, Loxo Oncology at Lilly is planning to study LOXO-305 in treatment-naïve CLL/SLL, including a global, randomized Phase 3 superiority clinical trial to study LOXO-305 versus ibrutinib, expected to start later in 2021.

About LOXO-305
LOXO-305 is an investigational, oral, highly selective, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including chronic lymphocytic leukemia, mantle cell lymphoma, Waldenström macroglobulinemia, and marginal zone lymphoma. Currently available BTK inhibitors irreversibly inhibit BTK and the long-term efficacy of these therapies can be limited by acquired resistance, most commonly through BTK C481 mutations. In rapidly growing tumors with inherently high rates of BTK turnover, resistance to covalent BTK therapies may be the result of incomplete target inhibition. LOXO-305 was designed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and avoid off-target kinases that have complicated the development of both covalent and investigational non-covalent BTK inhibitors. Interested patients and physicians can contact the Loxo Oncology at Lilly Physician and Patient BTK Clinical Trial Hotline at 1-855-LOXO-305 or email [email protected].

About the BRUIN Trial
This first-in-human, global, multi-center Phase 1/2 trial evaluates LOXO-305 as a single agent in patients with previously treated chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non-Hodgkin’s lymphomas (NHL). The trial includes a Phase 1 dose escalation phase and a Phase 2 dose expansion phase. The Phase 1 dose escalation enrolls patients with CLL/SLL or NHL who have received at least two prior lines of therapy and have progressed or are intolerant to standard of care. The dose escalation phase followed a "3+3" design with LOXO-305 dosed orally in 28-day cycles. As dose cohorts were cleared, additional patients could enroll in cleared cohorts and intra-patient dose escalation was permitted. The primary objective of the Phase 1 portion of the trial is to determine the maximum tolerated dose and recommended Phase 2 dose. Key secondary objectives include measures of safety, pharmacokinetics, and anti-tumor activity (i.e. Overall Response Rate (ORR) and Duration of Response, as determined by appropriate histology-specific response criteria). In the Phase 2, patients are enrolled across various cohorts, depending on disease type and prior therapy. The primary endpoint for Phase 2 is ORR. Secondary endpoints include duration of response (DOR), overall survival (OS), safety, and pharmacokinetics (PK).

About Loxo Oncology at Lilly
Loxo Oncology at Lilly was created in December 2019, combining the Lilly Research Laboratories oncology organization and Loxo Oncology, which was acquired by Lilly in early 2019. Loxo Oncology at Lilly brings together the focus and spirit of a biotech with the scale and resources of large pharma, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new oncology medicines that unequivocally work early in clinical development and will matter to patients.

On December 7, 2020 Seagen Inc. (Nasdaq:SGEN) reported multiple ADCETRIS (brentuximab vedotin) data presentations at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place virtually December 5-8, 2020 (Press release, Seagen, DEC 7, 2020, View Source [SID1234572321]). Data presentations include five-year updates from the phase 3 ECHELON-1 and ECHELON-2 clinical trials evaluating ADCETRIS plus a chemotherapy combination regimen in frontline advanced stage classical Hodgkin lymphoma (HL) and CD30-expressing frontline peripheral T-cell lymphoma (PTCL), respectively. In addition, first results were presented from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with Opdivo (nivolumab) in relapsed or refractory mediastinal gray zone lymphoma (MGZL), a rare type of non-Hodgkin lymphoma that express CD30 with no standard of care. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and expressed on the surface of several types of non-Hodgkin lymphoma, including PTCL. ADCETRIS is being evaluated globally in more than 70 corporate- and investigator-sponsored clinical trials across multiple settings in lymphoma and other indications. ADCETRIS and Opdivo are not approved alone or in combination for the treatment of relapsed or refractory MGZL.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"After five years of follow-up, an important clinical milestone, both the ECHELON-1 and ECHELON-2 clinical trials demonstrate that ADCETRIS plus chemotherapy resulted in superior and durable outcomes when compared with standard chemotherapy regimens," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "As most relapses in Hodgkin lymphoma occur within five years of frontline treatment, the results of the ECHELON-1 study suggest that patients treated with ADCETRIS plus chemotherapy are more likely to experience long-term remissions compared to those treated with the ABVD regimen."

Brentuximab Vedotin with Chemotherapy for Patients with Previously Untreated, Stage III/IV Classical Hodgkin Lymphoma: 5-Year Update of the ECHELON-1 Study (Abstract #2973, poster presentation on Monday, December 7, 2020)

The ECHELON-1 clinical trial is evaluating ADCETRIS in combination with AVD (Adriamycin [doxorubicin], vinblastine, dacarbazine) compared to ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine) in patients with Stage III or IV frontline classical HL. As previously reported, the ECHELON-1 trial achieved its primary endpoint with the combination of ADCETRIS plus AVD resulting in a statistically significant improvement in modified progression-free survival (PFS) compared to the control arm of ABVD as assessed by independent review facility (IRF; hazard ratio (HR), 0.77; p=0.035). A five-year exploratory analysis was conducted to examine PFS outcomes per investigator assessment in the intent-to-treat population of 1,334 patients. Results include:

Patients in the ADCETRIS plus AVD arm had a 32 percent reduction in the risk of a progression event compared to patients in the ABVD arm. The five-year PFS rate for patients in the ADCETRIS plus AVD arm was 82.2 percent compared to 75.3 percentin the ABVD arm, an absolute difference of 6.9 percent (HR, 0.681 [95% CI: 0.534, 0.867]). Median follow-up time was 60.9 months.
Consistent benefit in PFS was observed among patients treated with ADCETRIS plus AVD compared with ABVD, independent of disease stage, age and prognostic score.
Consistent improvements compared to ABVD were observed in patients with Stage III (HR, 0.593; [95% CI: 0.385, 0.915]) and Stage IV (HR, 0.731; [95% CI: 0.545, 0.980]) disease.
As previously reported for the primary analysis, on the ADCETRIS plus AVD arm, peripheral neuropathy events were observed in 67 percent of patients compared to 43 percent in the ABVD arm. The five-year update shows that among patients with peripheral neuropathy, 85 percent in the ADCETRIS plus AVD arm and 86 percent in the ABVD arm reported complete resolution or improvement at last follow-up.
There were fewer secondary malignancies in the ADCETRIS plus AVD arm. Among 48 patients with reported secondary malignancies, 19 [(nine hematological malignancies and 10 solid tumors)] were in the ADCETRIS plus AVD arm and 29 [(15 hematological malignancies and 14 solid tumors)] were in the ABVD arm.
There were a higher number of pregnancies in the ADCETRIS plus AVD arm compared to the ABVD arm. A total of 150 pregnancies were reported among study participants and their partners, including 89 on the ADCETRIS plus AVD arm and 61 on the ABVD arm.
The ECHELON-2 Trial: 5-Year Results of a Randomized, Double-Blind, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in Frontline Treatment of Patients with CD30-Positive Peripheral T-Cell Lymphoma (Abstract #1150, poster presentation on Saturday, December 5, 2020)

The ECHELON-2 clinical trial is evaluating ADCETRIS in combination with CHP (cyclophosphamide, Adriamycin [doxorubicin], prednisone) compared to CHOP (cyclophosphamide, Adriamycin [doxorubicin], vincristine, prednisone) in frontline CD30-expressing PTCL. As previously reported, the ECHELON-2 trial met its primary endpoint with the combination of ADCETRIS plus CHP resulting in a statistically significant improvement in PFS versus the control arm of CHOP per blinded independent central review (HR, 0.71; p=0.0110). A five-year post-hoc exploratory analysis was conducted to examine PFS outcome and overall survival (OS) per investigator assessment in the intent-to-treat population of 452 patients. Key findings include:

Patients in the ADCETRIS plus CHP arm had a 30 percent reduction in the risk of a progression event compared to patients in the CHOP arm. The five-year PFS rate for patients in the ADCETRIS plus CHP arm was 51.4 percent compared to 43 percent in the CHOP arm, an absolute difference of 8.4 percent (HR, 0.70 [95% CI: 0.53, 0.91]).
OS in the ADCETRIS plus CHP arm was improved compared to CHOP (HR=0.72 [95% CI: 0.53, 0.99]). This represents a 28 percent reduction in the risk of death. Median follow-up time was 66.8 months.
Among 316 systemic anaplastic large-cell lymphoma (sALCL) patients on study, patients in the ADCETRIS plus CHP arm had a 45 percent reduction in the risk of a progression event compared to patients in the CHOP arm (HR, 0.55 [95% CI: 0.39, 0.79]). There was a 34 percent reduction in the risk of death. Median follow-up time for PFS was 42.7 months.
Consistent improvement in both PFS and OS was observed among patients treated with ADCETRIS plus CHP arm compared to the CHOP arm across the majority of pre-specified subgroups.
The five-year update shows that among patients with peripheral neuropathy, 72 percent in the ADCETRIS plus CHP arm and 78 percent in the CHOP arm reported complete resolution or improvement at last follow-up. For ongoing peripheral neuropathy events, 98 percent in the ADCETRIS plus CHP arm and 98 percent in the CHOP arm were Grade 1 or 2.
Nivolumab Combined with Brentuximab Vedotin for Relapsed/Refractory Mediastinal Gray Zone Lymphoma: Primary Efficacy and Safety Analysis of the Phase 2 CheckMate 436 Study (Abstract #2045, poster presentation on Sunday, December 6, 2020)

Data from the ongoing CheckMate 436 phase 2 clinical trial of 10 patients with relapsed or refractory MGZL who received a combination of ADCETRIS plus Opdivo treatment after autologous stem cell transplant or two or more lines of multi-agent chemotherapy if ineligible for transplant will be presented for the first time. Patients were treated once every three weeks or until disease progression or unacceptable toxicity. The median age of patients was 35 years. Key findings include:

Of 10 response-evaluable patients, seven patients (70 percent) had an objective response, including five patients (50 percent) with a complete response and two patients (20 percent) with a partial response. Two patients (20 percent) had progressive disease and in one patient (10 percent) death occurred prior to disease assessment.
Median follow-up time was 12.4 months. Time to complete response was 1.2-4.8 months and the duration was 1.5+ to 3.2+ months before patients were assessed for subsequent therapy. All patients who achieved a complete response underwent a hematopoietic cell transplant and follow-up is ongoing.
The most common adverse events of any grade in at least 20 percent of patients were neutropenia and paresthesia (30 percent each); thrombocytopenia, anemia and peripheral sensory neuropathy (20 percent each). The most common Grade 3 adverse events were neutropenia and thrombocytopenia (10 percent each). Three patient deaths occurred due to disease progression.
About ADCETRIS

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seagen’s proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing cells.

ADCETRIS for injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions in 2013 for patients with (1) HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates and (2) sALCL after failure of at least one multi-agent chemotherapy regimen. Non-conditional approval was granted for (3) post-ASCT consolidation treatment of patients with HL at increased risk of relapse or progression in 2017, (4) adult patients with pcALCL or CD30-expressing MF who have received prior systemic therapy in 2018, (5) for previously untreated patients with Stage IV HL in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and (6) for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine (AVD), (2) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (3) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (4) for the treatment of adult patients with previously untreated sALCL in combination with cyclophosphamide, doxorubicin and prednisone (CHP), (5) for the treatment of adult patients with relapsed or refractory sALCL, and (6) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See U.S. important safety information, including Boxed Warning, below.

Seagen and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seagen has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seagen and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) U.S. Important Safety Information

BOXED WARNING

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

Contraindication

ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

Warnings and Precautions

Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Institute dose modifications accordingly.
Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.
Administer G-CSF primary prophylaxis beginning with Cycle 1 for patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL.

Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for bacterial, fungal, or viral infections.
Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid use in patients with severe renal impairment.
Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid use in patients with moderate or severe hepatic impairment.
Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.
Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.
Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.
Most Common (≥20% in any study) Adverse Reactions

Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, and mucositis.

Drug Interactions

Concomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE).

Use in Specific Populations

Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.