On May 26, 2022 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported positive results from the registration-enabling Phase 2 cohort of the KRYSTAL-1 study evaluating adagrasib 600 mg BID in patients with non-small cell lung cancer (NSCLC) harboring the KRASG12C mutation who have received at least one prior systemic therapy (Press release, Mirati, MAY 26, 2022, View Source [SID1234615094]). Findings will be presented on June 3 at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, as an oral presentation during the "Lung Cancer – Non-Small Cell Metastatic" session from 2:24 to 2:36 PM ET/ 1:24 to 1:36 PM CT (Abstract #9002).

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Summary of Clinical Results from Phase 2 Registration-Enabling Study
As of October 15, 2021, 116 patients were enrolled and treated in the study. Of the patients enrolled, 98% had prior treatment with a PD-1/L1 inhibitor following or in combination with chemotherapy. Median follow up was 12.9 months.
Of the patients evaluable for response (n=112), initial results showed that the objective response rate (ORR) by Blinded Independent Central Review (BICR) was 43%, the disease control rate (DCR) was 80%, the median duration of response (DOR) was 8.5 months (95% confidence interval [CI]: 6.2 – 13.8), and the median progression-free survival (PFS) was 6.5 months (95% CI: 4.7 – 8.4).
With a January 15, 2022 data cutoff, the median overall survival (OS) was 12.6 months (95% CI: 9.2 – 19.2).
The safety profile of adagrasib in this study was consistent with prior reports and no new safety signals were observed. The most frequent treatment related adverse events (TRAEs) included gastrointestinal events and fatigue. The majority of TRAEs were Grade 1–2 (53%) with Grade 3–4 TRAEs observed in 43% of patients. Two Grade 5 TRAEs were observed. TRAEs led to discontinuation of therapy in only 7% of patients.
"The positive and encouraging data from this trial further support the scientific rationale for targeting the KRASG12C mutation with adagrasib, which fully and continually inhibits mutant KRASG12C throughout the entire dosing period," says Alexander I. Spira, M.D., Ph.D., FACP, Co-Director, Virginia Cancer Specialists Research Institute. "This important dataset demonstrates positive clinical activity with adagrasib across molecular and clinical subgroups, including patients with treated and stable CNS metastases."

The Company also presented results from an exploratory, retrospective subgroup analysis from the Phase 2 NSCLC cohort of the KRYSTAL-1 study evaluating adagrasib in patients with KRASG12C-mutated NSCLC and stable, previously treated central nervous system (CNS) metastases (n=33). These results showed CNS-specific activity, including a 33% intracranial (IC) ORR by response assessment in neuro-oncology-brain metastases (modified RANO-BM). The IC DCR was 85% (95% CI: 68 – 95).

"The exploratory, retrospective subgroup analysis of adagrasib in patients with stable and previously treated CNS metastases showed intracranial tumor regression," added Dr. Spira. "These data are encouraging and contribute to the rapidly advancing science seeking to better understand how KRASG12C inhibitors like adagrasib can help improve patient outcomes."

Updated Findings from Pooled Analysis of KRYSTAL-1 NSCLC Cohorts
In addition to these results, the Company reported updated findings from a pooled analysis in a total of 132 patients from the KRYSTAL-1 study, including the registrational Phase 2 and Phase 1/1b NSCLC cohorts evaluating adagrasib at a dose of 600mg BID.

As of October 15, 2021, results from this pooled analysis showed an ORR of 44% and a disease control rate of 81% based on central independent review. The median DOR was 12.5 months and the median PFS was 6.9 months. With a January 15, 2022 data cutoff, (median duration of follow-up of 15.9 months) the median OS was 14.1 months. The safety and tolerability profile was consistent with the above reported findings for adagrasib in patients with advanced NSCLC. The Company plans to present full results from this pooled analysis at a future medical congress.

"The data from the registrational lung cancer cohort of KRYSTAL-1, including the clinical activity shown in patients with stable, previously treated CNS metastases, further support adagrasib’s unique profile," says Charles M. Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "Mirati is at the forefront of KRAS research, and we are pleased with the meaningfully positive clinical outcomes patients are experiencing with adagrasib, both in previously treated lung cancer and in other tumor settings."

On June 6, 2022, during an oral presentation at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting, the Company will present new, late-breaking results from the Phase 1b cohort of the KRYSTAL-1 study evaluating adagrasib in active, untreated CNS metastases (Abstract #LBA9009).

The adagrasib New Drug Application is currently being reviewed by the U.S. Food and Drug Administration (FDA) for Accelerated Approval (Subpart H) as a treatment for patients with NSCLC harboring the KRASG12C mutation who have received at least one prior systemic therapy. Adagrasib has also received Breakthrough Therapy Designation status from the FDA for the same indication. The Company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel who have been previously treated for metastatic NSCLC with a KRASG12C mutation.

Virtual Investor Event
Mirati Therapeutics will host an Investor Event on Monday, June 6, 2022, at 8:00 PM ET/7:00 PM CT.

Company executives will provide an overview of the adagrasib clinical data presented at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting and the Company’s broader lung cancer strategy, including in earlier lines of therapy.

Investors and the general public are invited to register and listen to a live webcast of the event through the "Investors and Media" section on Mirati.com. A replay of the event will be available shortly after the conclusion of the event.

Central Nervous System (CNS) Metastases in KRAS-Mutated Lung Cancer
The brain, along with the bone, adrenals, and liver are common sites of extra-thoracic metastases in NSCLC.[1]−3 CNS metastases occur in 27−42% of patients with KRASG12C-mutated NSCLC at diagnosis.1,4−6 Additionally, patients with CNS metastases and KRAS-mutated NSCLC may have poor outcomes, with median overall survival (OS) of approximately five months.7-9

About Adagrasib (MRTX849)
Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24–48 hours. Adagrasib is being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.

Mirati has an Expanded Access Program (EAP) for investigational adagrasib for the treatment of eligible patients with KRASG12C-mutated cancers, regardless of tumor type, including patients with treated or untreated CNS metastases, in the U.S. Learn more about the EAP at Mirati.com/expanded-access-policy.

On May 26, 2022 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that members of management will present at three upcoming investor conferences (Press release, Mersana Therapeutics, MAY 26, 2022, View Source [SID1234615093]). Details are as follows:

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Cowen’s 3rd Annual Oncology Innovation Summit

Jefferies Global Healthcare Conference

The JMP Securities Life Sciences Conference

A live webcast of these events will be available on the Investors & Media section of Mersana’s website at www.mersana.com. Archived replays will be available for approximately 90 days following the events.

On May 26, 2022 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, and Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company creating innovative medical solutions utilizing the latest biotechnology, reported that an abstract highlighting data and information from the Phase 2 TIDAL study evaluating the intermittent dosing of zandelisib, an investigational phosphatidylinositol 3-kinase delta ("PI3Kδ") inhibitor in clinical development for the treatment of B-cell malignancies, will be presented during a poster discussion session at the upcoming American Society of
Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting to be held June 3 – 7, 2022 (Press release, Kyowa Hakko Kirin, MAY 26, 2022, View Source [SID1234615092]).

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On May 26, 2022 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a biopharmaceutical company focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers, reported the presentation of the design and rationale of a Phase 1 trial-in-progress (KIN-4802, NCT05242822) evaluating the Company’s pan-FGFR inhibitor product candidate, KIN-3248 (Press release, Kinnate Biopharma, MAY 26, 2022, View Source [SID1234615091]). The details will be presented during a poster session on June 6, 2022, at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) taking place in Chicago, IL, June 3-7.

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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

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"A major limitation of approved and clinical-stage FGFR treatments is the emergence of secondary, on-target resistance mutations that reduce duration of response, highlighting the urgency to further research and develop more efficacious next-generation therapies for these patients," said the trial’s co-investigator and presenter Lipika Goyal, MD, a faculty member in Gastrointestinal Medical Oncology at Mass General Cancer Center. "We are pleased to share additional details of this two-part Phase 1 trial-in-progress evaluating KIN-3248 at this year’s ASCO (Free ASCO Whitepaper) conference."

KIN-3248 is an irreversible, small molecule pan-FGFR inhibitor designed to address primary FGFR2 and FGFR3 oncogenic alterations, and those predicted to drive acquired resistance to current FGFR-targeted therapies, including gatekeeper, molecular brake, and activation loop mutations observed in cancers such as intrahepatic cholangiocarcinoma (ICC) and urothelial carcinoma (UC). In preclinical studies, KIN-3248 demonstrated inhibitory activity across a wide range of clinically relevant mutations that drive primary disease and acquired resistance to other FGFR inhibitors.

The KN-4802 clinical trial (NCT05242822) is a multi-center, open-label, two-part study of approximately 120 patients to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of KIN-3248 in adults with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations. The dose escalation portion (Part A) of the trial will determine the recommended dose and schedule of KIN-3248 for further evaluation in patients with FGFR2 and/or FGFR3 gene alteration-driven cancers. The dose expansion phase (Part B) of the trial will assess the safety and efficacy of KIN-3248 at the recommended dose and schedule in FGFR inhibitor naïve and FGFR inhibitor pretreated patients with cancers driven by FGFR2 and/or FGFR3 gene alterations, including ICC, UC, and other selected adult solid tumors. This trial is currently enrolling across multiple sites in the United States.

"Unfortunately, acquired resistance to FGFR inhibitors frequently emerges during therapy for patients with FGFR-driven cancers, creating an urgent need to develop more effective and durable targeted therapies for these patients," said Richard Williams, MBBS, Ph.D., Chief Medical Officer of Kinnate. "We are pleased with the recent initiation of this first-in-human trial of KIN-3248, in collaboration with Mass General Cancer Center and other participating sites, and are grateful to the patients and physicians involved, without whom this research would not be possible."

In addition, in an abstract published in the ASCO (Free ASCO Whitepaper) meeting proceedings, the Company also shared updates from its preclinical in vitro and in vivo preclinical studies evaluating KIN-2787 in combination with binimetinib. In these studies, KIN-2787 demonstrated significant combination benefit in NRAS-mutant melanoma models. Taken together with its unique selectively, these data support the use of KIN-2787 in combination therapy in this patient segment. Melanoma tumor cell lines bearing NRAS Q61 alterations demonstrated synergistic benefit with KIN-2787 combined with binimetinib. Daily KIN-2787 plus binimetinib treatment in NRAS-altered melanoma xenograft models resulted in significant tumor growth inhibition benefit relative to either agent alone and was associated with added MAPK pathway biomarker suppression. A Phase 1/1b dose escalation and expansion clinical trial evaluating the safety and efficacy of KIN-2787 is ongoing (NCT04913285).

Abstracts accepted for the ASCO (Free ASCO Whitepaper) Annual Meeting include:

For additional information, visit the ASCO (Free ASCO Whitepaper) Annual Meeting webpage: View Source

Kinnate will also host an exhibit at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting at booth number 3047.

On May 26, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported promising initial data from a Phase 1/2 study evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis and subgroup analyses and molecular classification data from the SIENDO study evaluating selinexor in endometrial cancer (Press release, Karyopharm, MAY 26, 2022, View Source [SID1234615090]). These data, and four additional abstracts, will be presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO 2022), being held in Chicago from June 3-7, 2022.

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Results from Phase 1/2 Study Evaluating Selinexor in Combination with Ruxolitinib in Patients with Treatment-Naïve Myelofibrosis
The initial data to be presented at ASCO (Free ASCO Whitepaper) 2022 were based on the Phase 1 portion of the Phase 1/2 study evaluating the safety and preliminary efficacy of once-weekly selinexor in combination with standard dose ruxolitinib in patients with treatment-naïve myelofibrosis. As of May 1, 2022, 15 patients had been dosed with one of two dose levels of selinexor, 40 mg (n=3) and 60 mg (n=12), in combination with ruxolitinib 15/20 mg BID.

Seventy-five percent of evaluable patients (6 out of 8) demonstrated ≥35% reduction in spleen volume (SVR35) at week 12. Five out of 10 transfusion independent patients who had at least eight weeks of treatment maintained stable hemoglobin (± 2g/dL) or improved hemoglobin level (>2g/dL increase) at last follow up. In addition, all of the evaluable 7 patients, who had been at least 12 weeks on treatment and had complete data, experienced rapid reductions in their symptom scores with 3 of 7 patients having ≥50% reduction (TSS50) at week 12.

There were two patients who discontinued therapy in the trial: One patient discontinued after 5 months of therapy due to unrelated AEs (dizziness, atrial fibrillation, and pulmonary hypertension) and another patient discontinued after 8 weeks of therapy due to progression to AML.

The combination of selinexor and ruxolitinib was generally well-tolerated and manageable. No dose-limiting toxicities were reported at either dose level of selinexor, and the most common adverse event (AE) was nausea (40%), the majority of which were grade 1/2. Both the 40 mg and 60 mg dose levels were generally well tolerated, with the most common reported Grade 3-4 treatment-emergent AEs being thrombocytopenia (27%), anemia (20%), neutropenia (20%) and atrial fibrillation (20%). Hematologic adverse events were reversible with dose interruptions and reductions.

The trial is currently enrolling patients in the Phase 1b dose expansion part of the study.

"Despite tremendous improvements in the lives of patients with myelofibrosis with the introduction of the JAK inhibitors, there remains a significant unmet need. We are excited to develop a novel combination that may further improve outcomes for these patients," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "Following the promising initial results of selinexor in relapsed and refractory myelofibrosis, we are very excited with these preliminary data in treatment-naïve myelofibrosis patients in combination with ruxolitinib, with encouraging results seen across multiple measures including spleen volume reductions, improvements in symptom scores and management of anemia. We look forward to sharing these promising initial data with the broader medical and scientific community at ASCO (Free ASCO Whitepaper) 2022."

SIENDO Study Subgroup Analysis
A preliminary analysis of exploratory subgroups of the SIENDO study assessed four distinct molecular subtypes in endometrial cancer using The Cancer Genome Atlas (TCGA), one of the accepted gynecologic oncology algorithms that is used to calculate prognostic risk scores. This analysis indicated that patients with p53 wild-type endometrial cancer treated with selinexor showed a median progression-free survival of 13.7 months compared to 3.7 months for patients on placebo.

"These data suggest that selinexor may provide meaningful benefit to patients with p53 wild-type endometrial cancer and reinforce the need to further evaluate selinexor’s potential in a registration-enabling Phase 3 study, that we are planning to initiate in the second half of this year," added Dr. Rangwala.

Details for the ASCO (Free ASCO Whitepaper) 2022 selinexor presentations are as follows:
Oral Presentation

Title: Randomized phase III study of maintenance selinexor versus placebo in endometrial cancer (ENGOT – EN5/GOG-3055/SIENDO): Impact of subgroup analysis and molecular classification
Presenter: Vicky Makker, Memorial Sloan Kettering Cancer Center
Abstract #: 5511
Date and time: Tuesday, June 7, 2022, 9:48 a.m. – 10:00 a.m. EDT
Session: Clinical Science Symposium/Molecular-Based Treatment for Endometrial Cancer

Poster Presentations

Title: A phase 1, open-label, dose-escalation study of selinexor plus ruxolitinib in patients with treatment-naïve myelofibrosis
Presenter: Haris Ali, City of Hope
Abstract #: 7060
Date and time: Saturday, June 4, 2022, 9:00 a.m. – 12:00 p.m. EDT
Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Title: Phase Ib trial of selinexor (SEL) in combination with nivolumab (NIVO) alone or nivolumab plus ipilimumab (NIVO+IPI) in patients (pts) with advanced malignancies: The renal cell carcinoma (RCC) experience.
Presenter: Omar Alhalabi, The University of Texas MD Anderson Cancer Center
Abstract #: 4551
Date and time: Saturday, June 4, 2022, 2:15 p.m. – 5:15 p.m. EDT
Session: Genitourinary Cancer–Kidney and Bladder

Title: Phase 1b study of weekly split-dose selinexor in soft tissue sarcoma (STS)
Presenter: Abdulazeez Salawu, University Health Network
Abstract #: 11563
Date and time: Sunday, June 5, 2022, 9:00 a.m. – 12:00 p.m. EDT
Session: Sarcoma

Title: Digital monitoring and assessments in patients with glioblastoma
Presenter: Yasaman Damestani, Karyopharm Therapeutics, Inc.
Abstract #: 2045
Date and time: Sunday, June 5, 2022, 9:00 a.m. – 12:00 p.m. EDT
Session: Central Nervous System Tumors

Title: Phase Ib study of selinexor and eribulin combination in advanced solid tumors and triple-negative breast cancer
Presenter: Blessie Elizabeth Nelson, University of Texas MD Anderson Cancer Center
Abstract #: 3108
Date and time: Sunday, June 5, 2022, 9:00 a.m. – 12:00 p.m. EDT
Session: Developmental Therapeutics–Molecularly Targeted Agents and Tumor Biology

About the SIENDO Study
The Phase 3 SIENDO study (ENGOT-EN5/GOG-3055) is a multicenter, blinded, placebo-controlled, randomized study evaluating the efficacy and safety of selinexor as a maintenance therapy following chemotherapy in patients with advanced or recurrent endometrial cancer. The study enrolled 263 patients with primary stage IV or recurrent disease who had a partial or complete response after at least 12 weeks of standard taxane-platinum combination chemotherapy. Patients were randomized 2:1 to receive either maintenance therapy of 80mg of selinexor taken once weekly, or placebo, until disease progression. The primary endpoint of the study was statistically significant improvement of progression-free survival compared to placebo. The goal of the study was to demonstrate a hazard ratio of 0.6 or better. In partnership with Karyopharm, the study was initiated by the European Network for Gynaecological Oncological Trial (ENGOT) group. In the U.S., the collaboration includes the GOG Foundation, Inc. (GOG-F).

About XPOVIO (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea, Singapore and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including multiple myeloma, endometrial cancer and myelofibrosis. For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION
Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions were infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.