A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib vs Placebo Plus Ruxolitinib in Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib - KRT-232-115

Start Date19 Nov 2024

Sponsor / Collaborator

Kartos Therapeutics, Inc.

NCT06479135

/ RecruitingPhase 3

A Phase 3, Randomized, Double-blind, Add-on Study Evaluating the Safety and Efficacy of Navtemadlin Plus Ruxolitinib Vs Placebo Plus Ruxolitinib in JAK Inhibitor-Naïve Patients with Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib

This clinical trial is evaluating whether addition of navtemadlin to ruxolitinib treatment will provide more clinical benefit than ruxolitinib alone for patients with Myelofibrosis who have a suboptimal response to ruxolitinib treatment alone.
Subjects will start by receiving ruxolitinib alone in the run-in period. Those who demostrate a suboptimal response from ruxolitinib alone will then be randomized 2:1 to receive navtemadlin or navtemadlin placebo as add-on treatment to their ongoing ruxolitinib. Randomized means that subjects will be assigned to a group by chance, like a flip of a coin. The study is blinded, meaning the subjects, doctors, central endpoint assessors and sponsor will not know which add on treatment (navtemadlin or navtemadlin placebo) the subject is receiving.

Start Date03 Jun 2024

Sponsor / Collaborator

Kartos Therapeutics, Inc.

CTIS2022-502196-31-00

/ Not yet recruitingPhase 2/3

A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects with TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy - KRT-232-118

Start Date24 Aug 2023

Sponsor / Collaborator

Kartos Therapeutics, Inc.

100 Clinical Results associated with Navtemadlin

100 Translational Medicine associated with Navtemadlin

100 Patents (Medical) associated with Navtemadlin

Literatures (Medical) associated with Navtemadlin

19 Feb 2025·Science Translational Medicine

A window-of-opportunity trial reveals mechanisms of response and resistance to navtemadlin in patients with recurrent glioblastoma

Article

Author: Reynolds, Abigail R. N. ; Chakravarti, Arnab ; Beroukhim, Rameen ; Ye, Xiaobu ; Wen, Patrick Y. ; Sarosiek, Kristopher A. ; Bossi, Connor ; Pelton, Kristine ; Rudek, Michelle A. ; Ligon, Keith L. ; Cusick, Margaret ; Huang, Raymond Y. ; Sorger, Peter K. ; Pal, Sangita ; Desideri, Serena ; Ayoub, Georges ; Lapinskas, Emily ; Danda, Neeraja ; Fisher, Joy D. ; Palanichamy, Kamalakannan ; Walbert, Tobias ; Stopka, Sylwia A. ; Lee, Eudocia Q. ; Grossman, Stuart A. ; Khuu, Nicholas ; Lieberman, Frank ; Regan, Michael S. ; Holdhoff, Matthias ; Jeang, John ; Strowd, Roy ; Rashid, Rumana ; Lin, Jia-Ren ; Fassinou, Auriole C. R. ; Malinowski, Seth ; Santagata, Sandro ; Nabors, Louis B. ; Desai, Arati ; Spetz, Johan ; Agar, Nathalie Y. R. ; Azazmeh, Narmen ; Alexander, Brian M. ; Rendo, Veronica ; Pisano, William

Inhibitors of murine double minute homolog 2 (MDM2) represent a promising therapeutic approach for the treatment of TP53 wild-type glioblastomas (GBMs), reactivating p53 signaling to induce cancer cell death. We conducted a surgical window-of-opportunity trial (NCT03107780) of the MDM2 inhibitor navtemadlin (KRT-232) in 21 patients with TP53 wild-type recurrent GBM to determine achievable drug concentrations within tumor tissues and biological mechanisms of response and resistance. Participants received navtemadlin at 120 mg ( n = 10) or 240 mg ( n = 11) for 2 days before surgical resection and after surgery until progression or unacceptable toxicity. Both 120 and 240 mg daily dosing achieved a pharmacodynamic impact, but median progression-free survival was 3.1 months. DNA sequencing of three recurrent tumors revealed an absence of TP53 -inactivating mutations, indicating alternative mechanisms of resistance. To understand the mechanisms of response and resistance associated with navtemadlin, we conducted functional and spatial analyses of human tissue and patient-derived GBM neurosphere models. Navtemadlin induced partial tumor cell death as monotherapy, and combination with temozolomide enhanced apoptosis in GBM neurospheres while sparing normal bone marrow cells in vitro. We also observed up-regulation of oligodendrocyte differentiation genes with navtemadlin treatment and enrichment of oligodendrocyte transcription factor 2 (OLIG2)–positive cells at relapse, suggesting an unexplored mechanism of navtemadlin tolerance in GBM. Overall, these results indicated that clinically achievable doses of navtemadlin exert pharmacodynamic effects on GBM and suggest that combined treatment with temozolomide may be a route to more durable survival benefits.

01 Jan 2025·Computational and Structural Biotechnology Journal

Anticancer effects and mechanisms of Pulsatilla chinensis, Bupleurum chinense and Polyporus umbellatus on human lung carcinoma and hepatoma cells

Article

Author: Liu, Hongmin ; Song, Xiya ; Zhang, Cheng ; Turkez, Hasan ; Jin, Han ; Pan, Chengxue ; Uhlen, Mathias ; Yang, Hong ; Kim, Woonghee ; Fu, Ling ; Mardinoglu, Adil ; Kong, Xiangtai ; Li, Mengzhen ; Bi, Yuefeng

Herbs are extensively utilized in Traditional Chinese Medicine (TCM) for lung and liver cancer treatment, but the mechanisms behind these herbs remain largely unknown. Here, high-throughput transcriptomic analysis technology was used to uncover molecular mechanisms of herbal treatment. Furthermore, we developed a compound recognition approach utilizing the LINCS L1000 database to identify potential treatment targets. Our results showed that among 14 herbs tested, Pulsatilla chinensis exhibited the strongest anticancer effects in A549 and Huh7 cells, followed by Bupleurum chinense, and Polyporus umbellatus. P. chinensis exerts its anticancer properties by downregulating cell cycle-related transcription factors, including E2F1 and TFDP1. Notably, the mechanisms of P. chinensis treatment differed between the two cell lines. In A549 cells, which possess wild-type p53, P. chinensis induced apoptosis through the regulation of the p53 pathway. In contrast, in Huh7 cells, which harbor mutant p53, the effect was mediated via the TNF-α/NF-κB signaling pathway. We also identified two drugs, AMG232 and Nutlin-3, that exhibited treatment effects similar to P. chinensis in A549 cells. Both drugs function as inhibitors of the MDM2-p53 interaction. Western blot analysis confirmed the alteration of the relevant proteins, aligning with our computational predictions. Furthermore, 23-hydroxybetulinic acid, a key active compound of P. chinensis, demonstrated the ability to inhibit the p53-MDM2 interaction by binding to the same pocket on the MDM2 protein.

01 Nov 2024·FREE RADICAL BIOLOGY AND MEDICINE

Icariin targets p53 to protect against ceramide-induced neuronal senescence: Implication in Alzheimer's disease

Article

Author: Wu, Beibei ; Zhu, Lemei ; Xiao, Qiao ; Peng, Weijun ; Tang, Hanfen

BACKGROUND:

Alzheimer's disease (AD) is a leading cause of dementia. The aging brain is particularly vulnerable to various stressors, including increased levels of ceramide. However, the role of ceramide in neuronal cell senescence and AD progression and whether icariin, a natural flavonoid glucoside, could reverse neuronal senescence remain inadequately understood.

AIM:

In this study, we explore the role of ceramide in neuronal senescence and AD, and whether icariin can counteract these effects.

METHODS:

We pretreated HT-22 cells with icariin and then induced senescence with ceramide. Various assays were employed to assess cell senescence, such as reactive oxygen species (ROS) production, cell cycle progression, β-galactosidase staining, and expression of senescence-associated proteins. In vivo studies utilized APP/PS1 mice and C57BL/6J mice injected with ceramide to evaluate behavioral changes, histopathological alterations, and senescence-associated protein expression. Transcriptomics, molecular docking, molecular dynamics simulations, and cellular thermal shift assays were employed to verify the interaction between icariin and P53. The specificity of icariin targeting of P53 was further confirmed through rescue experiments utilizing the P53 activator Navtemadlin.

RESULTS:

Our data demonstrated that ceramide could induce neuronal senescence and AD-related pathologies, which were reversed by icariin. Moreover, molecular studies revealed that icariin directly targeted P53, and its neuroprotective effects were attenuated by P53 activation, providing evidence for the role of P53 in icariin-mediated neuroprotection.

CONCLUSION:

Icariin demonstrates a protective effect against ceramide-induced neuronal senescence by inhibiting the P53 pathway. This identifies a novel mechanism of action for icariin, offering a novel therapeutic approach for AD and other age-related neurodegenerative diseases.

News (Medical) associated with Navtemadlin

02 Mar 2023

·www.biospace.com

Kartos Therapeutics Appoints Dr. Srdan Verstovsek as Chief Medical Officer

World-Renowned Physician-Scientist and Global Expert in Myeloproliferative Neoplasms Will Be Instrumental in Advancing the Development of Navtemadlin and Other Innovative Therapies to Improve the Lives of Cancer Patients REDWOOD CITY, Calif.--(BUSINESS WIRE)-- Kartos Therapeutics, Inc. (“Kartos” or the “Company”), a clinical stage biopharmaceutical company dedicated to the development of novel, targeted therapeutics that meaningfully improve the lives of patients with cancer, today announced that Dr. Srdan (Serge) Verstovsek, MD, PhD, has been named Chief Medical Officer (CMO). Dr. Verstovsek is a world-renowned physician-scientist and a leading global authority on the treatment of myeloproliferative neoplasms (MPN), including myelofibrosis (MF). Since 1998, Dr. Verstovsek has been affiliated with the University of Texas MD Anderson Cancer Center where he served as hematologist-oncologist and more recently as the United Energy Resources, Inc. Professor of Medicine. He was also Director of the world’s largest MPN clinical research center, the Hanns A. Pielenz Clinical Research Center for MPNs, and Chief of the Section for MPNs. Dr. Verstovsek has collaborated extensively with Kartos in recent years and has been actively involved in all the company’s MPN clinical studies. In his new role, he will assume scientific leadership for the continued development of Kartos’ potential best-in-class MDM2 inhibitor, navtemadlin, currently in clinical development for the treatment of blood cancers and solid tumors, as well as other therapeutics the company is developing. Dr. Verstovsek has achieved international acclaim for pioneering practice-changing therapeutic advances for the treatment of MPNs. He has led more than 80 early/advanced phase clinical trials of novel MPN drugs, including ruxolitinib, which until 2019 was the only FDA-approved medication for myelofibrosis. He has published 24 book chapters, more than 600 peer-reviewed original articles/reviews in leading medical journals and has received numerous clinical research awards. “We are humbled that Dr. Serge Verstovsek has decided to continue his extraordinary career as part of the Kartos team,” said Jesse McGreivy, MD, Chief Executive Officer of Kartos Therapeutics. “Serge’s deep understanding of MPNs and his accomplishments as a clinician and drug developer are unparalleled. Having Serge onboard will be tremendously impactful in our quest to bring navtemadlin and other innovative medicines to patients across the globe.” “I am thrilled to join a Company so dedicated to developing novel, targeted therapeutics that meaningfully improve the lives of patients with cancer,” said Dr. Verstovsek. “Having worked closely with Kartos’ outstanding executive team and been deeply involved in designing several of the company’s studies, I know firsthand about the incredible talent and science driving the development of navtemadlin. I am very enthusiastic about the clinical potential of this groundbreaking drug and look forward to devoting the next stage of my career to help ensure its complete success.” Dr. Verstovsek is a member of the American Society for Clinical Investigation and is co-founder and an Executive Committee Member of the International Working Group for MF Treatment and Research. Dr. Verstovsek received his MD and PhD from the University of Zagreb, Croatia. About Kartos Therapeutics Kartos Therapeutics is a clinical stage biopharmaceutical company with a potential best-in-class MDM2 inhibitor, navtemadlin, in clinical development across a variety of TP53 wild-type hematological malignancies and solid tumors. To learn more, visit and connect with us on LinkedIn.

Drug ApprovalExecutive Change

06 Oct 2022

·www.biospace.com

Tempus Announces Companion Diagnostic Collaboration with Kartos Therapeutics

CHICAGO--(BUSINESS WIRE)-- Tempus a leader in artificial intelligence and precision medicine, today announced a new collaboration to develop a companion diagnostic (CDx) test with Kartos Therapeutics, a clinical stage biopharmaceutical company, in support of its ongoing Phase II study of navtemadlin (KRT-232). Tempus’ CDx test, which will be developed on Tempus’ xT platform, will be used to identify patients with TP53 wild-type (TP53WT) Merkel cell carcinoma (MCC) who may be eligible for treatment with navtemadlin. Navtemadlin is a potent, selective, orally available MDM2 inhibitor that overcomes MDM2 dysregulation by restoring p53 activity and inducing apoptosis of TP53WT tumor cells. Although rare, MCC is one of the most aggressive and lethal types of skin cancer, associated with a high risk of recurrence and metastasis, making it very difficult to treat. While anti-PD-1/L-1 antibodies have become standard of care for advanced or metastatic MCC, there remains an urgent need for effective therapies for patients who fail to respond, relapse or are intolerant to immunotherapy. Kartos is collaborating with Tempus to use the xT assay, a 648-gene panel, to identify patients with advanced or metastatic MCC who have retained functional (wild-type) TP53 and who have failed or are intolerant to anti-PD-1/L-1 immunotherapy. “We are pleased to be collaborating with the Tempus team to progress our goal of developing innovative therapies that meaningfully improve the lives of patients,” said Jesse McGreivy, MD, Chief Executive Officer and Chief Medical Officer at Kartos Therapeutics. “This partnership will allow us to develop a test to identify cancer patients who may benefit from treatment with navtemadlin; a therapy which offers a unique mechanism to restore the function of p53, one of the most critical tumor suppressor proteins, resulting in apoptosis of malignant cells in TP53WT MCC and other tumor types.” “Our proprietary platform provides a comprehensive suite of solutions for novel drug development programs while also giving physicians the data needed to make informed treatment decisions for their patients,” said Michael Yasiejko, Executive Vice President at Tempus. “We look forward to supporting Kartos’ diagnostic efforts in identifying cancer patients who could benefit from a more personalized approach to their treatment using a widely-available assay and clinician-friendly tools.” About Tempus Tempus is a technology company advancing precision medicine through the practical application of artificial intelligence in healthcare. With one of the world’s largest libraries of clinical and molecular data, and an operating system to make that data accessible and useful, Tempus enables physicians to make near real-time, data-driven decisions to deliver personalized patient care and in parallel facilitates discovery, development and delivery of optimal therapeutics. The goal is for each patient to benefit from the treatment of others who came before by providing physicians with tools that learn as the company gathers more data. For more information, visit tempus.com. About Kartos Therapeutics Kartos Therapeutics is a clinical stage biopharmaceutical company with a potential best-in-class MDM2 inhibitor, navtemadlin, that is in clinical development across a variety of TP53 wild-type hematological malignancies and solid tumors. To learn more, visit and connect with us on Twitter and LinkedIn.

CollaborateSmall molecular drugAntibodyImmunotherapy

22 Apr 2021

·www.biospace.com

Illumina and Kartos Therapeutics Announce New Oncology Partnership to Develop an NGS-Based TP53 Companion Diagnostic

April 22, 2021 20:05 UTC SAN DIEGO--(BUSINESS WIRE)--Illumina, Inc. (NASDAQ: ILMN) and Kartos Therapeutics, Inc. are pleased to announce a new partnership to co-develop a TP53 companion diagnostic (CDx) based on the content of Illumina’s comprehensive genomic profiling assay, TruSight™ Oncology 500 (TSO 500). This companion diagnostic for multiple hematologic indications will be the first to use TSO 500 with peripheral whole blood as a diagnostic sample type. “With this partnership, Illumina will expand the TruSight Oncology offerings into hematologic malignancies,” said Phil Febbo, MD, Chief Medical Officer of Illumina. “By leveraging our technology and harnessing the expertise at Kartos, we continue to advance Illumina’s commitment to develop standardized, globally distributable tools for precision oncology.” The initial focus of the collaboration will be the co-development of multiple CDx claims in blood cancers for Kartos’ KRT-232, a potent and selective oral MDM2 inhibitor that activates p53 to drive tumor cell death in TP53 wild-type cancers. “Kartos is dedicated to developing novel, targeted therapeutics that meaningfully improve the lives of patients with cancer,” said Jesse McGreivy, MD, Chief Executive Officer and Chief Medical Officer at Kartos. “This partnership will allow us to capitalize on TSO 500 as we explore the expanded use of KRT-232, which offers a unique mechanism to restore the function of p53, one of the most critical tumor suppressor proteins, resulting in apoptosis of malignant cells across a variety of hematologic and solid tumor types.” The collaboration with Kartos builds on a solid history and varied portfolio of Illumina’s oncology partnerships with industry leaders, with the united goal of advancing cancer diagnostics and precision medicine. About TruSight Oncology 500 TSO 500 is a Research Use Only comprehensive pan-cancer assay designed to identify 523 known and emerging tumor biomarkers. TSO 500 utilizes both DNA and RNA from tumor samples to identify key variants critical for cancer development and progression, such as small DNA variants, fusions, and splice variants. Based on the content of TSO 500, Illumina will be adding an in vitro diagnostic (IVD) test to the TruSight Oncology product family. This comprehensive tumor profiling assay will have similar chemistry and analytics to TSO 500. To learn more about TSO 500, click here. About Illumina Illumina is improving human health by unlocking the power of the genome. Our focus on innovation has established us as the global leader in DNA sequencing and array-based technologies, serving customers in the research, clinical, and applied markets. Our products are used for applications in the life sciences, oncology, reproductive health, agriculture, and other emerging segments. To learn more, visit and connect with us on Twitter, Facebook, LinkedIn, Instagram, and YouTube. About Kartos Therapeutics Kartos Therapeutics is a clinical stage biopharmaceutical company with a potential best-in-class MDM2 inhibitor (KRT-232) in clinical development, across a variety of TP53 wild-type hematological malignancies and solid tumors. To learn more, visit and connect with us on Twitter and LinkedIn. Use of forward-looking statements This release contains forward-looking statements that involve risks and uncertainties, including the expectation for lower costs related to the storing and managing of genomic data costs. Among the important factors that could cause actual results to differ materially from those in any forward-looking statements are: (i) challenges inherent in developing and launching new products and services; (ii) our ability to deploy new products, services, and applications, and to expand the markets for our technology platforms; and (iii) the acceptance by customers of our newly launched products, which may or may not meet our and their expectations once deployed, together with other factors detailed in our filings with the Securities and Exchange Commission, including our most recent filings on Forms 10-K and 10-Q, or in information disclosed in public conference calls, the date and time of which are released beforehand. We undertake no obligation, and do not intend, to update these forward-looking statements, to review or confirm analysts’ expectations, or to provide interim reports or updates on the progress of the current quarter.

Collaborate

100 Deals associated with Navtemadlin

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Endometrial Cancer	Phase 3	United States	Kartos Therapeutics, Inc.	17 Jul 2023
Recurrent Endometrial Cancer	Phase 3	Austria	Kartos Therapeutics, Inc.	17 Jul 2023
Recurrent Endometrial Cancer	Phase 3	Canada	Kartos Therapeutics, Inc.	17 Jul 2023
Recurrent Endometrial Cancer	Phase 3	Denmark	Kartos Therapeutics, Inc.	17 Jul 2023
Recurrent Endometrial Cancer	Phase 3	Estonia	Kartos Therapeutics, Inc.	17 Jul 2023
Recurrent Endometrial Cancer	Phase 3	Finland	Kartos Therapeutics, Inc.	17 Jul 2023
Recurrent Endometrial Cancer	Phase 3	Georgia	Kartos Therapeutics, Inc.	17 Jul 2023
Recurrent Endometrial Cancer	Phase 3	Hungary	Kartos Therapeutics, Inc.	17 Jul 2023
Recurrent Endometrial Cancer	Phase 3	Israel	Kartos Therapeutics, Inc.	17 Jul 2023
Recurrent Endometrial Cancer	Phase 3	Italy	Kartos Therapeutics, Inc.	17 Jul 2023

Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03041688 (PF504, EHA2025)	Phase 1	Acute Myeloid Leukemia TP53-unmutated	37	Navtemadlin	yhrcgoyuqp(pnzstlvoyl) = adrsbnraof fjofyxefqq (iwbsqygxkq ) View more	Positive	14 May 2025
NCT03041688 (PF504, EHA2025)	Phase 1	Acute Myeloid Leukemia TP53-unmutated	37	Decitabine	yhrcgoyuqp(pnzstlvoyl) = bdlqkhsfls fjofyxefqq (iwbsqygxkq ) View more	Positive	14 May 2025
NCT03107780 (NEWS \| Pubmed) Manual	Phase 1	Recurrent Glioblastoma TP53野生型	21	Navtemadlin 120mg/240mg	rajxhihapy(wumfvfcmrx) = ntryebrjoh mslfnzhwco (gqsnkfohbh )	Positive	27 Feb 2025
ASH2024	Not Applicable	Myelofibrosis	-	Navtemadlin 240 mg once-daily	trdlblculi(hkijwszbcv) = wywbxxclyf agsgkrfcru (udxnzyftun ) View more	-	09 Dec 2024
ASH2024	Not Applicable	Myelofibrosis	-	Best Available Therapy (BAT)	trdlblculi(hkijwszbcv) = zqjkdgmhsb agsgkrfcru (udxnzyftun ) View more	-	09 Dec 2024
NCT04485260 (EHA2023)	Phase 1/2	Primary Myelofibrosis	32	Navtemadlin + Ruxolitinib	vytvjgzapc(txptmbvpfy) = ximgpmtmcn oghngdupav (nqgytghcek ) View more	-	08 Jun 2023
NCT03662126 (BOREAS, EHA2023)	Phase 3	Mycosis Fungoides	113	Nvtm 120 mg QD	oxpkkaothj(estgkpeums) = sbfnuygkzs klwonxyqsh (llxqpjxkwu ) View more	-	08 Jun 2023
NCT03787602 (NOTOS, ASCO2023)	Phase 1/2	Merkel Cell Carcinoma	-	Navtemadlin 180 mg QD	ihaobtnvpm(jtwscexous) = tgnqyertha xccylublkw (ptvvpajkuq ) View more	Positive	31 May 2023
NCT03787602 (ASCO2022) Manual	Phase 1/2	Merkel Cell Carcinoma TP53 Wild-type	29	Navtemadlin 240 mg (7D on/ 14D off)	zqawpzymyn(uufcveaeop) = axtkolifew xfkikoaqan (fagxxleqqc ) View more	Positive	02 Jun 2022
NCT03787602 (ASCO2022) Manual	Phase 1/2	Merkel Cell Carcinoma TP53 Wild-type	29	Navtemadlin 240 mg (5D on/ 23D off)	zqawpzymyn(uufcveaeop) = thiflwsugi xfkikoaqan (fagxxleqqc ) View more	Positive	02 Jun 2022
NCT03217266 (NRG-DT001, ASCO2022) Manual	Phase 1	Soft Tissue Sarcoma Neoadjuvant	-	Navtemadlin	iaiwqkgsuz(gdzcjxyyss) = 120 mg 5x/week fudyzacjdl (uarxdrsyxz )	Positive	02 Jun 2022
NCT02110355 (Pubmed) Manual	Phase 1	Metastatic melanoma TP53-wild type	31	dabrafenib+trametinib+AMG 232	znakyauhds(orrlbjggws) = kemrqhalzg hsrqkquojq (nddlnhzdao ) View more	Positive	30 May 2022
NCT02110355 (Pubmed) Manual	Phase 1	Metastatic melanoma TP53-wild type	31	trametinib	znakyauhds(orrlbjggws) = kymqvffwgy hsrqkquojq (nddlnhzdao ) View more	Positive	30 May 2022
NCT01723020 (Pubmed \| Invest New Drugs) Manual	Phase 1	Advanced Malignant Solid Neoplasm \| Multiple Myeloma TP53 Wild-type	107	AMG 232	mirbzytswn(wrloebyjow) = diarrhea, nausea, vomiting, fatigue, decreased appetite, and anemia rbjncywpht (cdkqettoxl ) View more	Positive	01 Jun 2020

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