iSTAR: Phase 1b Trial of Idasanutlin and Selinexor Therapy For Children With Progressive/Relapsed Atypical Teratoid Rhabdoid Tumors, Extra-CNS Malignant Rhabdoid Tumors Or Synchronous/Metachronous Rhabdoid Tumors

iSTAR is an open-label, multi-center, phase 1b study of oral XPO1 inhibitor selinexor and oral MDM2 inhibitor idasanutlin in children with progressive or recurrent atypical teratoid/rhabdoid tumors (AT/RT), malignant rhabdoid tumors (MRT) and synchronous/metachronous rhabdoid tumors.
Primary Objectives
To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of combination treatment with oral idasanutlin and selinexor in children with recurrent or progressive AT/RT or MRT.
To characterize the plasma pharmacokinetics of oral idasanutlin and selinexor in children with recurrent or progressive AT/RT or MRT, to assess potential covariates to explain the inter- and intra-individual pharmacokinetic variability.
Secondary Objectives
Evaluate safety of the combination treatment with oral idasanutlin and selinexor in children
Evaluate efficacy of the combination treatment of idasanutlin and selinexor as measured by objective response (partial response [PR] or complete response [CR]) rate separately in progressive/relapsed AT/RT and progressive/relapsed MRT
Estimate progression-free and overall-survival separately in progressive/relapsed AT/RT and progressive/relapsed MRT

Start Date01 Mar 2024

Sponsor / Collaborator

St. Jude Children's Research Hospital, Inc.

NCT04589845 / RecruitingPhase 2

Tumor-Agnostic Precision Immunooncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial

TAPISTRY is a Phase II, global, multicenter, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in rational, specified combinations in participants with unresectable, locally advanced or metastatic solid tumors determined to harbor specific oncogenic genomic alterations or who are tumor mutational burden (TMB)-high as identified by a validated next-generation sequencing (NGS) assay. Participants with solid tumors will be treated with a drug or drug regimen tailored to their NGS assay results at screening. Participants will be assigned to the appropriate cohort based on their genetic alteration(s). Treatment will be assigned on the basis of relevant oncogenotype, will have cohort-specific inclusion/exclusion criteria, and, unless otherwise specified, will continue until disease progression, loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first.

Start Date18 Jan 2021

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

NCT04029688 / CompletedPhase 1/2

A Phase I/II, Multicenter, Open-Label, Multi-Arm Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in the Treatment of Pediatric and Young Adult Patients With Relapsed/Refractory Acute Leukemias or Solid Tumors

This is a Phase I/II, multicenter, open-label, multi-arm study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of idasanutlin, administered as a single agent or in combination with chemotherapy or venetoclax, in pediatric and young adult participants with acute leukemias or solid tumors.
This study is divided into three parts: Part 1 will begin with dose escalation of idasanutlin as a single agent in pediatric participants with relapsed or refractory solid tumors to identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and to characterize dose-limiting toxicities (DLTs). Following MTD/MAD identification, three separate safety run-in cohorts in neuroblastoma, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) will be conducted to identify the recommended Phase 2 dose (RP2D) of idasanutlin in each combination, with chemotherapy or venetoclax. Part 2 will evaluate the safety and early efficacy of idasanutlin in combination with chemotherapy or venetoclax in newly enrolled pediatric and young adult participants in neuroblastoma, AML,and ALL cohorts at idasanutlin RP2D. Part 3 will potentially be conducted as an additional expansion phase of the idasanutlin combination cohorts in neuroblastoma, AML, or ALL for further response and safety assessment.

Start Date27 Jan 2020

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

100 Clinical Results associated with Idasanutlin

100 Translational Medicine associated with Idasanutlin

100 Patents (Medical) associated with Idasanutlin

107

Literatures (Medical) associated with Idasanutlin

01 Dec 2024·LEUKEMIA

Managing the unmanageable: evidence-driven approaches to real-world patient prototypes of TP53-mutant myelodysplastic neoplasms and acute myeloid leukemia

Review

Author: Patel, Shyam A ; Patel, Shyam A.

Patients with TP53 aberrations comprise the highest risk subset of all myeloid malignancies. The managerial conundrum of TP53-mutant myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) stems from refractoriness to or relapse after conventional chemotherapy, as well as the limited translational success of investigational therapies targeting TP53-mutant cells. Thus far, no targeted therapies have been commercially approved for this mutational subset. As a result, management plans for patients with TP53-mutant MDS and AML are often driven by clinical judgment and/or physician preference rather than consensus guidelines backed by a rigorous evidence basis. This clinical case-based, evidence-driven review highlights the most salient data that guides the management of commonly encountered patient prototypes. This review discusses the therapeutic menu of first-line options that derive from multi-institutional experiences as well as from disease-centric consortia and discusses how these first-line options can be optimally tailored to heterogeneous groups of patients. The debate regarding whether allogeneic stem cell transplant should be offered to these patients is summarized. Finally, this review explores the recent unfortunate news of pauses in clinical trials for the leading investigational agents - eprenetapopt, magrolimab, sabatolimab, and idasanutlin - and offers solutions toward re-invigorating the pipeline of precision therapeutics in 2025.

01 Dec 2024·INVESTIGATIONAL NEW DRUGS

Targeting MDM2-mediated suppression of p53 with idasanutlin: a promising therapeutic approach for acute lymphoblastic leukemia

Article

Author: Gungordu, Seyda ; Aptullahoglu, Erhan

Despite available treatments for acute lymphoblastic leukemia (ALL), the disease's high clinical variability necessitates new therapeutic strategies, particularly for patients with high-risk features. The tumor suppressor protein p53, encoded by the TP53 gene and known as the guardian of the genome, plays a crucial role in preventing tumor development. Over 90% of ALL cases initially harbor wild-type TP53. Reactivation of p53, which is encoded from the wild type TP53 but lost its function for several reasons, is an attractive therapeutic approach in cancer treatment. p53 can be activated in a non-genotoxic manner by targeting its primary repressor, the MDM2 protein. Clinical trials involving MDM2 inhibitors are currently being conducted in a growing body of investigation, reflecting of the interest in incorporating these treatments into cancer treatment strategies. Early-phase clinical trials have demonstrated the promise of idasanutlin (RG7388), one of the developed compounds. It is a second-generation MDM2-p53 binding antagonist with enhanced potency, selectivity, and bioavailability. The aim of this study is to evaluate the efficacy of RG7388 as a therapeutic strategy for ALL and to investigate its potential impact on improving treatment outcomes for high-risk patients. RG7388 potently decreased the viability in five out of six ALL cell lines with diverse TP53 mutation profiles, whereas only one cell line exhibited high resistance. RG7388 induced a pro-apoptotic gene expression signature with upregulation of p53-target genes involved in the intrinsic and extrinsic pathways of apoptosis. Consequently, RG7388 led to a concentration-dependent increase in caspase-3/7 activity and cleaved poly (ADP-ribose) polymerase. In this research, RG7388 was investigated with pre-clinical methods in ALL cells as a novel treatment strategy. This study suggests further functional research and in-vivo evaluation, and it highlights the prospect of treating p53-functional ALL with MDM2 inhibitors.

01 Oct 2024·APOPTOSIS

Strong activation of p53 by actinomycin D and nutlin-3a overcomes the resistance of cancer cells to the pro-apoptotic activity of the FAS ligand

Article

Author: Rusin, Marek ; Łasut-Szyszka, Barbara ; Będzińska, Agnieszka ; Gdowicz-Kłosok, Agnieszka ; Głowala-Kosińska, Magdalena ; Krześniak, Małgorzata

Abstract:

The FAS ligand (FASLG) is expressed on lymphocytes, which employ it to activate death receptors on target cells. Cancer cells are generally resistant to apoptosis triggered by FASLG. In this work, we found a way to circumvent this resistance by treatment with actinomycin D (ActD) and nutlin-3a (Nut3a). We selected this drug combination based on our transcriptomic data showing strong activation of proapoptotic genes, including those for receptor-mediated apoptosis, in cells exposed to actinomycin D and nutlin-3a. To test our hypothesis, we pre-exposed cancer cell lines to this drug combination for 45 h and then treated them with recombinant FASLG. This almost instantaneously killed most cells. Actinomycin D and nutlin-3a strongly cooperated in the sensitization because the effect of the drugs acting solo was not as spectacular as the drug combination, which together with FASLG killed more than 99% of cells. Based on the caspase activation pattern (caspase-8, caspase-9, caspase-10), we conclude that both extrinsic and intrinsic pro-apoptotic pathways were engaged. In engineered p53-deficient cells, this pro-apoptotic effect was completely abrogated. Therefore, the combination of ActD + Nut3a activates p53 in an extraordinary way, which overcomes the resistance of cancer cells to apoptosis triggered by FASLG. Interestingly, other combinations of drugs, e.g., etoposide + nutlin-3a, actinomycin D + RG7112, and actinomycin D + idasanutlin had a similar effect. Moreover, normal human fibroblasts are less sensitive to death induced by ActD + Nut3a + FASLG. Our findings create the opportunity to revive the abandoned attempts of cancer immunotherapy employing the recombinant FAS ligand.Graphical Abstract

News (Medical) associated with Idasanutlin

12 Apr 2021

·www.globenewswire.com

Global Acute Myeloid Leukemia (AML) Disease Analysis Report 2021: On Average, it Takes 10.8 Years from Phase I to Approval, Compared to 9.6 Years in the Overall Oncology Space

Dublin, April 12, 2021 (GLOBE NEWSWIRE) -- The "Disease Analysis: Acute Myeloid Leukemia (AML)" report has been added to ResearchAndMarkets.com's offering. AML is a type of heterogeneous hematological malignancy that originates from immature white blood cells (blasts) in the bone marrow, which may be derived from either a hematopoietic stem cell or a lineage-specific progenitor cell. "Acute" means that the leukemia may progress rapidly - AML generally spreads quickly to the bloodstream and can then spread to other parts of the body including the lymph nodes, spleen, central nervous system, and testicles.Latest Key TakeawaysThe publisher estimates that in 2018, there were 158,400 incident cases of acute myeloid leukemia (AML) worldwide and expects that number to increase to 169,000 incident cases by 2027. Approximately 60% of newly diagnosed patients are eligible for intensive chemotherapy, such as the 7+3 regimen of cytarabine and daunorubicin.Since 2017, there have been nine new drugs approved for AML in the US, dramatically changing the treatment landscape. Gone is the era where all front-line patients received either 7+3 chemotherapy or a hypomethylating agent (decitabine or azacitidine). Many of the new therapies target specific segments of AML or patients with specific mutations. As such, there is currently little competition between the new therapies, but that will change as therapies receive label expansions and new competitor therapies are approved.Two FLT3 inhibitors have been approved for FLT3-mutated AML: Rydapt for front-line patients eligible for intensive chemotherapy, and Xospata for relapsed/refractory patients. Rydapt may soon face competition in the front-line FLT3 setting as quizartinib, crenolanib, and Xospata are being evaluated in combination with standard chemotherapy and as single-agent maintenance therapies following either chemotherapy consolidation or hematopoietic stem cell transplant (HSCT). Approval in the lucrative maintenance setting would give these drugs a favorable long-term commercial outlook. Approximately 25-30% of AML patients have an FLT3 mutation.Tibsovo and Idhifa are approved in the US as oral, single-agent therapies for relapsed/refractory AML patients with IDH1 and IDH2 mutations, respectively. Tibsovo is also approved as a monotherapy for front-line patients over the age of 75 years. Both of these IDH inhibitors are now in Phase III trials in combination with standard induction (7+3) and consolidation chemotherapy and as maintenance therapy in front-line AML. Tibsovo is also being investigated in combination with azacitidine in a Phase III trial in front-line patients. Approval of Tibsovo and Idhifa in the EU will depend on these Phase III results. Tibsovo may face competition from FT-2102, an IDH1 inhibitor being evaluated in the relapsed/refractory setting in a pivotal single-arm Phase II trial. IDH1 mutations are present in 6-9% of AML, while IDH2 mutations are present in approximately 12% of cases.Mylotarg, an antibody-drug conjugate targeting CD33, is the only monoclonal antibody therapy approved for AML. Mylotarg combined with intensive chemotherapy is recommended for newly diagnosed patients with favorable cytogenetic risk (approximately 10% of patients eligible for intensive chemotherapy). Over 90% of AML patients are positive for CD33 expression.Vyxeos, a liposomal formulation of the 7+3 chemotherapy regimen, was approved in the US and EU for the treatment of newly diagnosed patients with secondary AML after showing an improvement in overall survival compared to the 7+3 regimen in patients ?60 years of age. Secondary AML accounts for approximately one third of new AML diagnoses, but most of these patients will be too frail for Vyxeos. Approximately 16% of patients eligible for intensive chemotherapy have secondary AML. Market access for Vyxeos is strengthened by positive recommendations from the US Centers for Medicare and Medicaid Services and from NICE in England and Wales.Venclexta combined with azacitidine is the new standard of care for newly diagnosed AML patients not suited for intensive chemotherapy (approximately 40% of newly diagnosed patients). A confirmatory Phase III trial evaluating Venclexta + azacitidine demonstrated a survival advantage (15 months versus 10 months) and supported regulatory submissions to European and Japanese authorities, with approvals expected in 2021. Venclexta is currently being evaluated in combination with novel agents in several trials, and a Phase III study (VIALE-M) is evaluating Venclexta combined with azacitidine as maintenance therapy for AML patients in first remission after conventional chemotherapy.Daurismo is the first and only Hedgehog pathway inhibitor approved for AML. Daurismo is approved in combination with low-dose cytarabine (LDAC) for newly diagnosed AML patients not suited for intensive chemotherapy, and will compete with Venclexta in this difficult-to-treat setting. However, in the US, hypomethylating agents are preferred over LDAC, so Venclexta may be preferred over Daurismo.Onureg, an oral formulation of azacitidine, increased overall survival and relapse-free survival in a Phase III trial and was approved in the US as a maintenance therapy following intensive chemotherapy for patients not suited for an HSCT. A European approval decision is expected in mid-2021. The maintenance setting would be a new setting for Vidaza (azacitidine) which is currently used in the EU (and off-label in the US) to treat newly diagnosed elderly AML patients.Rafael Pharmaceuticals is developing devimistat (CPI-613) as a first-in-class therapeutic targeting the altered mitochondrial metabolism present in many cancers, including AML. Devimistat's outlook will depend on the efficacy and safety results from a Phase III trial evaluating the drug in combination with high-dose cytarabine and mitoxantrone in relapsed/refractory AML patients. The first interim analysis is expected in Q2 2021.Chimerix's dociparstat sodium (DSTAT), a glycosaminoglycan analog of heparin designed to have reduced anticoagulant effects, targets the CXCR4 pathway which is involved in the homing and adhesion of AML cells to the bone marrow and is associated with resistance to systemic drugs. DSTAT is being developed in combination with intensive 7+3 chemotherapy for newly diagnosed AML, with the aim of improving the rate of durable response. A Phase III trial is enrolling patients with intermediate or unfavorable cytogenetic risk (74% of patients eligible for intensive chemotherapy).Otsuka's Inqovi is an oral formulation of decitabine that is being developed for patients with AML unsuited for intensive induction chemotherapy. In ASCERTAIN, a Phase III trial enrolling patients with MDS, Inqovi met the trial's primary endpoint of demonstrating pharmacokinetic equivalence to intravenous decitabine. ASCERTAIN has now been extended to include patients with AML in the EU, but a trial with efficacy endpoints will be needed to secure a US AML approval.Takeda's pevonedistat targets the NEDD8-activating enzyme in the ubiquitin-proteasome pathway, and is being developed in combination with azacitidine for a subpopulation of newly diagnosed, elderly AML patients categorized as low-blast count AML. Pevonedistat is also being evaluated in a randomized Phase II trial in combination with Venclexta and azacitidine in newly diagnosed AML patients unfit for intensive chemotherapy.Zeltherva is a therapeutic vaccine being developed as maintenance therapy for patients who have achieved hematologic complete remission, with or without thrombocytopenia, after second-line therapy and who are ineligible for allogeneic stem cell transplantation. Zeltherva's outlook in the specialized setting of CR2 will depend on results in REGAL, its Phase III trial. An interim analysis for safety and futility is expected in Q4 2021.Not including FLT3 and IDH inhibitors, there are five drugs in late-phase development for newly diagnosed AML patients. Dociparstat sodium and entospletinib are being developed in combination with intensive chemotherapy, while MBG453, pevonedistat, and Inqovi are being developed for elderly patients.Relapsed/refractory AML remains an area of unmet need, and new therapies are being developed. Not including FLT3 or IDH inhibitors, there are currently five late-stage therapies being evaluated for this setting (devimistat, DFP-10917, flotetuzumab, Iomab-B, and uproleselan).Key recent events include the approval of Onureg and presentation of numerical data from Venclexta's VIALE-A trial. There were Phase III failures for Helsinn's pracinostat combined with azacitidine in the newly diagnosed setting and for Roche's idasanutlin and Otsuka's guadecitabine in the relapsed/refractory setting. Other Phase III failures include trials evaluting Xospata combined with azacitidine and Daurismo combined with intensive chemotherapy in front-line AML, and an Idhifa monotherapy trial in the third- and fourth-line setting.Key upcoming catalysts for 2021 include topline results from Phase III trials for devimistat, Iomab-B, uproleselan, and Zeltherva, and a possible NDA submission for FT-2102.The overall likelihood of approval of a Phase I AML asset is 6.3%, and the average probability a drug advances from Phase III is 50%. AML drugs, on average, take 10.8 years from Phase I to approval, compared to 9.6 years in the overall oncology space. Companies Mentioned For more information about this report visit

AntibodyFirst in ClassVaccineADC

07 Apr 2021

·www.biospace.com

Rain Plans $100 Million IPO, Phase III Trial for Lead Precision Cancer Therapy

Newark, California-based cancer company Rain Therapeutics filed Friday for a $100 million IPO to advance its lead MDM2 inhibitor RAIN-32 into Phase III testing. The news comes months after the company closed a $63 million Series B and inlicensed RAIN-32 from Daiichi Sankyo. Rain licenses and develops precision cancer therapies. The new lead program, RAIN-32, previously completed Phase I testing in patients with solid tumors or lymphomas. The influx of cash will support a pivotal Phase III trial in liposarcoma, which Rain intends to launch this year, plus two more Phase II trials in solid tumors and intimal sarcoma, respectively. Preclinical data published by independent French researchers last year suggested MDM2 inhibitors had therapeutic potential for treating liposarcomas, where MDM2 amplification is common. MDM2 is an inhibitor of tumor-suppressive p53, a notoriously challenging drug target. Several companies are developing MDM2 inhibitors to act upstream of p53, with limited success, which Rain attributes to dose-limiting hematological toxicities. Last year, Roche ended development of its MDM2 inhibitor, idasanutlin, then in Phase II testing for patients with acute myeloid leukemia (AML). The most advanced anti-MDM2 therapy is APG-115, which Ascentage Pharma has in multiple Phase Ib/II trials for solid tumors and hematologic malignancies, plus a Phase II combination trial with checkpoint inhibitor Keytruda (pembrolizumab) for anti-PD-1 refractory or relapsed cancers. At least two other companies–Novartis and Aileron–also have MDM2 inhibitors in early clinical testing for several cancers. According to Rain, the safety and tolerability data from Daiichi Sankyo’s trial suggest RAIN-32 can be dosed longer than other MDM2-targeting programs in development. Rain also has a preclinical RAD52 inhibitor program, licensed from Drexel University in August 2020. RAD52 plays a role in DNA damage response and the company is exploring therapies for breast and ovarian cancers characterized by BRCA1/2 mutations. The company is aiming to select a lead clinical RAD52 inhibitor candidate in 2022. There are no known RAD52 inhibitors in clinical trials. As recently as last year, its previous lead candidate tarloxotinib, licensed from the University of Auckland, was in Phase II testing for patients with EGFR and ErbB Exon 20 insertion mutations in solid tumors. The company has not announced an end to the trial but tarloxotinib is not named in Rain’s Securities and Exchange Commission (SEC) forms or listed on the company’s website. Rain did not respond to a request for clarification in time for publication.

IPO

04 Feb 2021

·www.biospace.com

Roche Washes Hands of Mid and Late-Stage Trial Failures

Jonathan Weiss / Shutterstock Roche is closing out its fourth-quarter with some house cleaning. The Swiss pharma giant announced in its earnings report that it was terminating studies of several mid- and late-stage assets, including two late-stage breast cancer programs. In its fourth-quarter presentation, Roche noted several programs that have been terminated after earlier clinical trial failures in 2020. Roche included a checklist for ongoing programs and the ones that have been terminated included a large, red X. One of the studies terminated is the Phase III IMagyn050 trial assessing a combination of two previously approved cancer drugs. The study was seeking to determine if adding Tecentriq (atezolizumab) to a combination of Avastin (bevacizumab), paclitaxel and carboplatin would make a difference in the treatment of women with newly diagnosed advanced-stage ovarian cancer. It did not. The addition of Tecentriq did not improve progression-free survival to the first-line combination therapy. Another program terminated is the Phase III IPATunity130 study. That trial was assessing ipatasertib, an Akt inhibitor, and chemotherapy for the treatment of patients with PIK3CA/AKT1/PTEN-altered hormone receptor-positive, HER2-negative advanced breast cancer. The trial failed to meet its endpoints of both progression-free survival and objective response rate. AKT1/2/3, which ipatasertib inhibits, is the central node of the PI3K/AKT pathway, which plays a critical role in HR-positive, HER2-negative breast cancer. Although ipatasertib missed the mark in the breast cancer study, Roche is still investigating its use in other cancers. Last year, the asset hit the mark in the Phase III IPATential150 study in patients with metastatic castration-resistant prostate cancer whose tumors had PTEN loss. Ipatasertib in combination with abiraterone and prednisone/prednisolone provided a statistically significant reduction in the risk of disease worsening or death, the company said at the time. The other Phase III program culled by Roche is a combination of idasanutlin, an MDM2 antagonist, and chemotherapy for the treatment of acute myeloid leukemia. The combination failed to reach endpoints of improving survival in the late-stage MIRROS program. Roche had hoped to determine if the addition of idasanutlin to chemotherapy would prove superior to chemotherapy alone. The addition of the MDM2 antagonist did not prolong life in those patients. Although idasanutlin failed in the MIRROS trial, Roche and Genentech are investigating it along with Venclexta in patients with relapsed or refractory AML who are not eligible for chemotherapy. It wasn’t just late-stage programs that saw the proverbial axe. Roche also terminated two mid-stage programs in ulcerative colitis and autism spectrum disorder. Roche subsidiary Genentech reported etrolizumab demonstrated a mixed bag in a Phase III ulcerative colitis test. While the drug hit its endpoint of inducing remission versus placebo, it failed to meet its primary endpoint versus placebo as maintenance therapy in people with ulcerative colitis. The autism study that Roche terminated involved an asset that received Breakthrough Therapy designation in 2018. Last year, Roche announced it was terminating the trial assessing balovaptan, a vasopressin 1a (V1a) receptor antagonist. Roche stopped the Phase II study of balovaptan early last year following a futility assessment. In its fourth-quarter report, Roche said sales in its Pharmaceuticals Division decreased 2% to CHF 44.5 billion, mainly due to stronger than expected biosimilars competition and the COVID-19 pandemic. Sales in the U.S. slipped 6%. Roche said biosimilars for blue-chip assets MabThera/Rituxan, Herceptin and Avastin were particularly impacted by biosimilars. Tecentriq sales increased mainly due to growth in the new indications, including certain forms of lung, breast and liver cancer, the company said. Most Read Today

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100 Deals associated with Idasanutlin

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Refractory acute myeloid leukemia	Phase 3	US	Hoffmann-La Roche, Inc.	30 Dec 2015
Refractory acute myeloid leukemia	Phase 3	AU	Hoffmann-La Roche, Inc.	30 Dec 2015
Refractory acute myeloid leukemia	Phase 3	AT	Hoffmann-La Roche, Inc.	30 Dec 2015
Refractory acute myeloid leukemia	Phase 3	BE	Hoffmann-La Roche, Inc.	30 Dec 2015
Refractory acute myeloid leukemia	Phase 3	CA	Hoffmann-La Roche, Inc.	30 Dec 2015
Refractory acute myeloid leukemia	Phase 3	FI	Hoffmann-La Roche, Inc.	30 Dec 2015
Refractory acute myeloid leukemia	Phase 3	FR	Hoffmann-La Roche, Inc.	30 Dec 2015
Refractory acute myeloid leukemia	Phase 3	DE	Hoffmann-La Roche, Inc.	30 Dec 2015
Refractory acute myeloid leukemia	Phase 3	IL	Hoffmann-La Roche, Inc.	30 Dec 2015
Refractory acute myeloid leukemia	Phase 3	IT	Hoffmann-La Roche, Inc.	30 Dec 2015

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02670044 (Pubmed) Manual	Phase 1	Acute Myeloid Leukemia	50	Venetoclax+idasanutlin	fqtopmwswg(egnknoiydk) = diarrhea (87.3% of patients), nausea (74.5%), vomiting (52.7%), hypokalemia (50.9%), and febrile neutropenia (45.5%) apxwbzvptr (akppiktndb )	Positive	20 Oct 2022
NCT03850535 (CTgov)	Phase 1/2	Acute Myeloid Leukemia	24	daunorubicin+idasanutlin+cytarabine (Dose-Escalation Cohort 1)	gqclhvcjbg(dadnekntzz) = gjleloovum izwqyujxtd (rghmaiuwjj, fozmwjlqqo - qqlnuflgap) View more	-	21 Jun 2022
				daunorubicin+idasanutlin+cytarabine (Dose Escalation Cohort 2)	gqclhvcjbg(dadnekntzz) = kjsqpeqvza izwqyujxtd (rghmaiuwjj, twiwayoeea - xfwuohkmsx) View more
NCT02545283 (MIRROS, Pubmed \| Blood Adv) Manual	Phase 3	Acute Myeloid Leukemia First line \| Second line \| Third line	447	Cytarabine+Idasanutlin	quxjzujayd(btblibpnwp) = mtxyovtviq xtixmyiewg (ipxthmtoyp ) View more	Negative	12 Apr 2022
				Cytarabine+Placebo	quxjzujayd(btblibpnwp) = pquipgrmmu xtixmyiewg (ipxthmtoyp ) View more
NCT03287245 (Pubmed) Manual	Phase 2	Polycythemia Vera	16	Idasanutlin	qgnsqzohyv(aglecxeech) = sgdbothgnj hqkxvcvwot (vjzkjhhljr ) View more	Positive	22 Feb 2022
NCT02545283 (MIRROS, CTgov)	Phase 3	Relapsing acute myeloid leukemia \| Refractory acute myeloid leukemia	447	Placebo+Cytarabine (Placebo Plus Cytarabine)	lezvgjugab(tpnydlmcce) = axhjrxvhyc tichwzphhq (umkkzgdaoy, sntoajvunn - qinricoyke) View more	-	14 Sep 2021
				Idasanutlin+Cytarabine (Idasanutlin Plus Cytarabine)	lezvgjugab(tpnydlmcce) = rnmbhvwhtc tichwzphhq (umkkzgdaoy, vezmdebpki - ylbetjbxru) View more
NCT03566485 (CTgov)	Phase 1/2	Metastatic breast cancer \| Estrogen receptor positive breast cancer \| Breast Cancer 3 ... View more	12	Cobimetinib+Atezolizumab	tssgvoqykq(qutzywqsnh) = rxpbduwjyd jlrzskhcmd (xqfqhfdvqu, dpmevqlkcf - noqappzqxb) View more	-	11 Aug 2021
NCT01773408 (Pubmed \| Leuk Res) Manual	Phase 1	Acute Myeloid Leukemia	122	overall	ryautkvfvd(zdtcatutee) = The RDE was determined as 600 mg twice a day for the MBP formulation and 300 mg twice a day for the SDP formulation. gkscuisywx (egoaslyamx ) View more	Positive	01 Jan 2021
				cytarabine+Idasanutlin (TP53 wild-type pts)
NCT03135262 (ASH2020) Manual	Phase 1/2	Non-Hodgkin's lymphoma refractory	29	Idasanutlin+Venetoclax+Obinutuzumab	udbkzsmigf(jsqegwiwzf) = 48.3% [neutropenia (10.3%)] mpgpdhaiqa (tfsfmpwnvk ) View more	Positive	05 Nov 2020
NCT02624986 (BH29812, EHA2020)	Phase 2	Follicular Lymphoma \| Diffuse Large B-Cell Lymphoma	25	Idasanutlin + Obinutuzumab	jaqealsjyo(cvdmzpyvex) = All FL or DLBCL pts had ≥ 1 AE. 79.2% had ≥ 1 Grade 3/4 AEs, most commonly thrombocytopenia (75%), neutropenia (62.5%) and anaemia (37.5%). No Grade 5 AEs were reported. 37.5% of pts experienced SAEs, most commonly febrile neutropenia (8.3%) and diarrhoea (8.3%). Dose-limiting toxicity events were all Grade 3/4 thrombocytopenia. 37.5% of pts had an AE leading to withdrawal of study treatment, most commonly thrombocytopenia (25%) and neutropenia (8.3%). yvyubizhks (idxxjhliud )	-	14 May 2020
				Idasanutlin + Rituximab
NCT02670044 (ASH2019) Manual	Phase 1	Refractory acute myeloid leukemia	49	Venetoclax+Idasanutlin	fssqewgqei(jcwfydgkxu) = febrile neutropenia (45%), neutropenia (27%), and thrombocytopenia (25%) ppqerfiexf (rtzfnoacro ) View more	Positive	13 Nov 2019

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