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Turning Point Therapeutics Announces Updated Interim Clinical Data of Repotrectinib in Advanced ROS1+ Non-Small Cell Lung Cancer

On May 31, 2019 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing novel drugs to address treatment resistance, reported updated interim data from its ongoing Phase 1/2 TRIDENT-1 clinical study of lead drug candidate repotrectinib in ROS1-positive non-small cell lung cancer (NSCLC) patients (Press release, Turning Point Therapeutics, MAY 31, 2019, View Source [SID1234536729]).

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The results, which will be presented today during an oral session at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), demonstrate ongoing antitumor activity and a manageable safety profile across multiple dose cohorts in both tyrosine kinase inhibitor (TKI) naïve and TKI-pretreated patients, including patients with intracranial disease.

"With additional follow up and new patients enrolled in the TRIDENT-1 study, repotrectinib continues to demonstrate promising efficacy and a safety profile consistent with a potential best-in-class ROS1 therapy for patients with advanced non-small cell lung cancer," said Dr. Byoung Chul Cho, Yonsei Cancer Center at Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. "The ongoing Phase 1 data remain encouraging in both TKI-naïve patients with intracranial disease and patients pretreated with crizotinib — including those with difficult to treat solvent front mutations — where there are currently very few therapeutic options."

Dr. Cho is an investigator for the TRIDENT-1 study and will present the data today at the annual ASCO (Free ASCO Whitepaper) conference.

Repotrectinib is an investigational next-generation TKI designed to effectively target ROS1 and TRK A/B/C and systemically overcome resistant mutations that invariably result following treatment with other TKIs. ROS1 rearrangement is an oncogenic driver of tumors in up to 2.6 percent of U.S. advanced NSCLC patients.

As of the March 4, 2019 data cut-off, the interim Phase 1 data showed the following results.

Preliminary Safety Analysis (n=83):

A total of 83 (ROS1+, NTRK+ and ALK+) patients were treated with repotrectinib at dose levels from 40 mg daily (QD) to 200 mg twice daily (BID).
Repotrectinib was generally well tolerated, with the most frequent treatment emergent adverse events (TEAEs) being Grade 1 or 2. The TEAEs found in >25% of pts were dizziness (57%), dysgeusia (51%), dyspnea (30%), fatigue (30%), constipation (29%), paresthesia (29%), and anemia (28%). There were few Grade 3 treatment-related AEs (anemia (n=3); dizziness (n=2); and dyspnea, hypophosphatemia, hypoxia, pleural effusion, and weight increase (all n=1)), and no Grade 4 treatment-related AEs or cases of dizziness leading to treatment discontinuation.
No additional dose-limiting toxicities (DLTs) have occurred since the last data cut-off of Oct. 31, 2018. Prior DLTs included Grade 3 dyspnea/hypoxia (n=1), and Grade 2 (n=1) and Grade 3 (n=2) dizziness. Four total Grade 5 TEAEs (one of four determined to be possibly treatment related) have occurred, with one Grade 5 case of respiratory failure reported as related to disease progression since the last interim data update.
Preliminary Efficacy Analysis (n=33)

Within the ROS1+ NSCLC blinded independent central review (BICR) efficacy evaluable population (n=33), the median number of prior TKI therapies was one (range 0 to 3), the majority of which were crizotinib.
Forty-five percent of patients remained on treatment (15/33), with 12 of the 15 (80%) patients remaining on treatment for more than 12 months.
TKI-Naïve Efficacy Analysis

In TKI-naïve patients, overall response rate (ORR) by BICR was 82 percent (9/11). At a dose of 160 mg QD or above, the likely recommended Phase 2 dose, ORR by BICR remains at 83 percent, consistent with the prior update. Efficacy results are summarized in the following table:

Prior Interim Analysis by BICR
Oct. 31, 2018 Data cut-off Current Interim Analysis by BICR
March 4, 2019 Data cut-off
All ROS1 NSCLC (TKI
Naïve & Pretreated) N=28 N=33
TKI Naïve N=10 N=11
Median Follow up –
(Range) 16.4 months
(5.3-16.6+) 16.4 months
(3.5+-19.4+)
ORR (%)
(95% CI) 9/10 (90)
(56-100) 9/11 (82)
(48-98)
ORR at 160 mg QD or
above 5/6 (83) 5/6 (83)
Median Duration of
Response – Months
(Range) Not Reached
(5.5+-14.9+)
5 of 9 remain in cPR
(5.5+ to 14.9+ months) Not Reached
(5.6-17.7+)
5 of 9 remain in cPR (10.9+ to 17.7+ months)
Intracranial ORR n (%)
(95% CI) 3/3 (100)
(29-100) 3/3 (100)
(29-100)
All remain in cPR
Clinical Benefit Rate (%)
(95% CI) 10/10 (100)
(69-100) 11/11 (100)
(72-100)
TKI-Pretreated Efficacy Analysis

In TKI-pretreated patients, ORR by BICR improved from 28 percent in the prior data cut-off to 32 percent, and from 44 percent to 55 percent in patients pretreated with 1 TKI and dosed at 160 mg QD or above. Efficacy results are summarized in the following table:

Prior Interim Analysis by BICR
Oct. 31, 2018 Data cut-off Current Interim Analysis by BICR
March 4, 2019 Data cut-off
All ROS1 NSCLC (TKI Naïve
& Pretreated) N=28 N=33
TKI Pretreated N=18 N=22
Median Follow up –
(Range) 12.9 months
(0.6-14.5) 14.6 months
(1.4-16.6+)
ORR (%)
(95% CI) 5/18 (28)
(10-53) 7/22 (32)
(14-55)

O
R
R

1 prior TKI 5/15 (33) 7/18 (39)
1 prior TKI
160 mg QD or above 4/9 (44) 6/11 (55)
1 prior TKI
crizotinib only
160 mg QD or above 3/6 (50) 4/7 (57)
2 or more prior TKIs 0/3 (0) 0/4 (0)
Duration of Response –
Months
# still in response (+) 1 of 5 responders still in cPR at 1.9+ months 3 of 7 responders still in cPR at 1.0+ to 7.6+ months
ORR in G2032R Solvent
Front Mutations
(%) 1/4 (25) 2/5 (40)
Intracranial ORR n (%)
1 prior TKI 2/4 (50)
2/3 (67) 3/5 (60)
3/4 (75)
Clinical Benefit Rate (%)
(95% CI) 14/18 (78)
(52-94) 16/22 (73)
(50-89)
Five patients pretreated with crizotinib had a ROS1 G2032R solvent front mutation detected at baseline by plasma cfDNA or next-generation sequencing tests. All five patients had tumor regressions, including two confirmed partial responses (cPR) at the 160 mg QD dose level.

"Since first reporting preliminary TRIDENT-1 interim data for repotrectinib at the 2018 annual ASCO (Free ASCO Whitepaper) meeting, we are very pleased to see the results continue to strengthen with each subsequent data cut-off while maintaining a consistent safety profile in both TKI-naïve and TKI-pretreated ROS1+ NSCLC patients," said Athena Countouriotis, M.D., president and chief executive officer. "The current treatment options for patients with ROS1+ advanced non-small cell lung cancer are limited, particularly when resistance develops to other TKIs. We look forward to finalizing our recommended Phase 2 dose and beginning the registrational portion of TRIDENT-1 in the second half of this year."

Financial Update
The company separately filed its Form 10-Q today for the first quarter of 2019. Operating expenses during the first quarter were $14.1 million compared to $4.9 million in the first quarter of 2018. The $9.2 million increase was primarily due to increased personnel expenses and activities for the development of repotrectinib, TPX-0022 and TPX-0046. Net cash used in operating activities was $10.2 million, an increase from $5.4 million in the prior-year period.

Turning Point expects expenses will increase through the year as it plans to initiate up to four clinical trials in 2019 including: the Phase 2 TRIDENT-1 registrational study for repotrectinib; a Phase 1/2 study of repotrectinib in pediatric patients with advanced solid tumors with NTRK, ALK, or ROS1 alterations; a Phase 1 dose-finding study for TPX-0022, a novel MET, CSF1R and SRC inhibitor in patients with advanced solid tumors harboring genetic alterations in MET; and, pending completion of IND-enabling studies, a Phase 1 study of TPX-0046, a novel RET and SRC inhibitor in patients with advanced solid tumors with oncogenic RET genetic alterations.

Cash and cash equivalents at March 31 were $90 million. In addition, the company raised net proceeds of $175.2 million from its April 2019 initial public offering. The company projects its cash position will be sufficient to fund current operations into the second half of 2021.

OncoArendi Therapeutics at the 2019 BIO International Convention in USA

On May 31, 2019 OncoArendi Therapeutics will present and promote its programs during the 2019 BIO International Convention in Philadelphia, USA, recognized as one of the world’s most important events in the biotechnology and pharmaceutical industry. Over 16,000 participants from 67 countries will attend the conference (Press release, OncoArendi Therapeutics, MAY 31, 2019, View Source [SID1234536728]).

OncoArendi represented by: Marcin Szumowski, CEO, Nicolas Beuzen, Director of Business Development and Pawel Dobrzanski, Senior Scientific Director has over 40 formally accepted meetings, during which two of the Company’s most advanced assets will be presented:

OATD-01, a drug developed in inflammation-driven fibrotic diseases currently completing phase Ib of clinical development, as well as
OATD-02, an arginase inhibitor for cancer treatment, currently completing IND-enabling studies.
– During this event we will meet new prospects potentially interested in global or regional (i.e. Asian) rights, and continue ongoing discussions, initiated at previous events, some already under confidentiality agreements. At the same time scouting will be conducted to identify novel molecules that could complement our portfolio of early stage programs – says Marcin Szumowski, CEO OncoArendi Therapeutics.

– We are keeping our eye on the global biotechnology market that grows at an increasing pace. Many new innovative ideas appear in areas directly related to research projects currently pursued by OncoArendi. Inhibitors of deubiquitinases, a family of proteins representing potential targets in cancer therapy is just one example. These targets have been recently pursued by several mid-size biotech companies, confirming the attractiveness of these new molecular targets in treatment of various diseases.

Updated Results of Studies in Advanced Cervical Cancer and Melanoma Support Long-Term Efficacy of Iovance Tumor Infiltrating Lymphocyte (TIL) Therapy

On May 31, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported updated data from studies of TIL therapy LN-145 in patients with advanced cervical cancer and TIL therapy lifileucel in advanced melanoma (Press release, Iovance Biotherapeutics, MAY 31, 2019, View Source;p=RssLanding&cat=news&id=2400232 [SID1234536727]). At 7.4-month median follow-up in the ongoing study of LN-145 in advanced cervical cancer, an 11 percent complete response rate (CR) was seen. Furthermore, the median duration of response (DOR) had not been reached. At 8.8-month median follow-up in the ongoing study of lifileucel in advanced melanoma, median duration of response had not been reached. Updated data from the ongoing innovaTIL-04 and innovaTIL-01 studies will be presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper).

"As we continue to observe the effects of Iovance TIL therapy, we have not yet reached a median DOR for our TIL product in either our melanoma or cervical trial," commented Maria Fardis, Ph.D., president and chief executive officer of Iovance Biotherapeutics. "We are also extremely encouraged to see CRs in our cervical cancer study as the study continues over time, demonstrating the potential for deep responses after one treatment. The same phenomenon was noted in our melanoma trial as well with two CRs now being reported at ASCO (Free ASCO Whitepaper) in a heavily pre-treated melanoma patient population."

"The duration of response of current second line treatments for advanced cervical cancer are in the range of three to five months and options are limited," commented Emese Zsiros, M.D., Ph.D., faculty researcher at the Department of Gynecologic Oncology of the Roswell Park Comprehensive Cancer Center and Iovance LN-145 study investigator. "The observation in the study of LN-145 that median DOR has not yet been reached at a median of 7.4 months following treatment provides evidence that this therapy could provide a clinically meaningful improvement over currently available options for patients with advanced cervical cancer."

As of May 14, 2019, data from the innovaTIL-04 study in 27 patients with recurrent, metastatic or persistent cervical cancer demonstrated an objective response rate of 44 percent (3 complete responses and 9 partial responses) and a disease control rate of 85 percent. At 7.4-month median follow-up, 10 patients maintained a response and the median DOR had not been reached (range 2.6+ to 9.2+ months). The mean patient age was 45 years and study participants had experienced a mean of 2.4 prior lines of therapy. Study data will be presented on Saturday, June 1 (Abstract #2538, Poster 182).

As of May 8, 2019, results from Cohort 2 in the ongoing innovaTIL-01 study demonstrated an ORR of 38 percent (2 complete responses and 23 partial responses) in 66 consecutively dosed post-PD-1 patients with Stage IIIC/IV unresectable melanoma. In this study, patients had experienced a mean of 3.3 lines of prior therapy including anti-PD1 blocking antibody, and the patients had a high baseline tumor burden. The disease control rate was 80 percent. At 8.8-month median follow-up, median DOR had not been reached (range 1.4+ to 19.8+ months). Study data will be presented on Saturday, June 1 (Abstract #2518, Poster 162).

Iovance Biotherapeutics to Participate in Upcoming Conferences in June

On May 31, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that the company plans to participate in the following conferences in June (Press release, Iovance Biotherapeutics, MAY 31, 2019, View Source;p=RssLanding&cat=news&id=2400226 [SID1234536726]):

Showcasing Greater Philadelphia’s Life Sciences & Innovation Assets at BIO 2019 in Philadelphia, June 3, 2019
Location: Comcast Technology Center
Date/Time: Monday, June 3, 2019, from 3:30 p.m. – 6:30 p.m. EDT
Jefferies 2019 Healthcare Conference in New York, June 4-7, 2019
Corporate overview
Location: Grand Hyatt New York
Date/Time: Wednesday, June 5, at 11:30 a.m. EDT
A live and archived webcast of the presentation will be available by visiting the Investors section of the Iovance Biotherapeutics website at View Source

Session: Best of ASCO (Free ASCO Whitepaper) Panel
Location: Grand Hyatt New York
Date/Time: Thursday, June 6, from 12:15 p.m. – 1:15 p.m. EDT
24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Amsterdam, June 13-16, 2019
Poster: Iovance Peripheral Blood Lymphocytes (PBL): A Potential Cell Therapy Strategy For The Treatment Of Chronic Lymphocytic Leukemia
Authors: Lavakumar Karyampudi et al.
Session: Gene therapy, cellular immunotherapy and vaccination – Biology & Translational Research
Abstract Number: PF447
Location: RAI Amsterdam
Date/Time: Friday, June 14, from 5:30 p.m. – 7:00 p.m. CEST

KITE AND HUMANIGEN ANNOUNCE CLINICAL COLLABORATION TO EVALUATE INVESTIGATIONAL COMBINATION OF YESCARTA® (AXICABTAGENE CILOLEUCEL) WITH LENZILUMAB IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA

On May 31, 2019 Kite, a Gilead Company (Nasdaq: GILD) and Humanigen, Inc., (HGEN) reported the formation of a clinical collaboration to conduct a Phase 1/2 study of lenzilumab, an investigational anti-GM-CSF monoclonal antibody, with Yescarta (axicabtagene ciloleucel) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Press release, Humanigen, MAY 31, 2019, View Source [SID1234536725]). The objective of this study is to determine the effect of lenzilumab on the safety of Yescarta. Kite will act as the sponsor of this study and will be responsible for its conduct.

GM-CSF has been identified, through clinical correlative analysis and preclinical modeling, as a potential key signal in the inflammatory cascade triggering toxicities associated with chimeric antigen receptor T (CAR T) cell therapy.1 Toxicities associated with CAR T therapy include neurologic toxicity and cytokine release syndrome (CRS). Emerging pre-clinical evidence suggests that lenzilumab inhibition of GM-CSF may have the potential to disrupt CAR T cell mediated inflammation without disrupting CAR T cell anti-tumor efficacy.

"CAR T therapy represents a significant advance in the way relapsed or refractory large B-cell lymphoma is treated," said John McHutchison, AO, MD, Chief Scientific Officer, Head of Research and Development, Gilead. "As leaders in cell therapy, we are committed to pursuing a number of clinical and preclinical strategies aimed at further improving the efficacy and safety of CAR T therapy. We look forward to this clinical collaboration with Humanigen and to evaluating the combination of lenzilumab and Yescarta in our clinical trial."

1Sterner, R., Sakemura, R., Cox, M., Yang, N., Khadka, R., Forsman, C.,… Kenderian, S. (2019).
GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts. Blood : the official journal of the American Society of Hematology (ASH) (Free ASH Whitepaper), 133:697-709. doi: View Source

"Humanigen has pioneered the approach to neutralizing GM-CSF to improve CAR T," said Cameron Durrant, MD, Chief Executive Officer, Humanigen. "This collaboration with Kite will help validate the work Humanigen has done in understanding the pathophysiology of the inflammatory cascade as well as the potential role GM-CSF plays in influencing CAR T cell treatment outcomes."

Yescarta was the first CAR T cell therapy to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, and high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of cytokine release syndrome and neurologic toxicities; see below for Important Safety Information.

Lenzilumab, alone or in combination with other therapies such as Yescarta, is investigational and has not been approved by the FDA or any regulatory authority for any uses. Efficacy and safety have not yet been established.

Stifel, Nicolaus & Company, Incorporated acted as exclusive financial advisor to Humanigen in this transaction.

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

·Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
·Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
·Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS.

CYTOKINE RELEASE SYNDROME (CRS): CRS occurred in 94% of patients, including 13% with ≥ Grade 3. Among patients who died after receiving Yescarta, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to infusion of Yescarta. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES: Neurologic toxicities occurred in 87% of patients. Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks, with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade 3 or higher occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures occurred with Yescarta. Fatal and serious cases of cerebral edema have occurred in patients treated with Yescarta. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities. Monitor patients for signs or symptoms of neurologic toxicities for 4 weeks after infusion and treat promptly.

YESCARTA REMS: Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS. The required components of the Yescarta REMS are: Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer Yescarta are trained about the management of CRS and neurologic toxicities. Further information is available at www.YESCARTAREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS: Allergic reactions may occur. Serious hypersensitivity reactions including anaphylaxis may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in Yescarta.

SERIOUS INFECTIONS: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients, and in 23% with ≥ Grade 3. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Yescarta infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. Grade 3 or higher cytopenias not resolved by Day 30 following Yescarta infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after Yescarta infusion.

HYPOGAMMAGLOBULINEMIA: B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS: The most common adverse reactions (incidence ≥ 20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.