Last update 26 Dec 2024

Danvatirsen

Last update 26 Dec 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

ASO

Synonyms

Danvatirsen-sodium, IONIS-STAT3RX, ISIS-STAT3RX

+ [9]

Target

STAT3

Mechanism

STAT3 inhibitors(Signal transducer and activator of transcription 3 inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesCongenital Disorders+ [5]

Active Indication

Squamous Cell Carcinoma of Head and NeckAdvanced Colorectal AdenocarcinomaAdvanced Lung Non-Small Cell Carcinoma+ [11]

Inactive Indication

Advanced cancerAdvanced Hepatocellular CarcinomaDiffuse Large B-Cell Lymphoma+ [2]

Originator Organization

Ionis Pharmaceuticals, Inc.

Active Organization

Flamingo Therapeutics BVStartup

AstraZeneca PLC

Dynacure SAStartup

Inactive Organization

MedImmune LLC

Ionis Pharmaceuticals, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Gene Sequence

Sequence Code 526076414

Source: *****

Clinical Trials associated with Danvatirsen

NCT05986240 / RecruitingPhase 1IIT

A Phase I Study Investigating the Safety & Efficacy of Danvatirsen as Monotherapy Followed by Combination With Venetoclax in Patients With Relapsed/Refractory MDS & AML

This is a Phase 1 study investigating the safety and efficacy of Danvatirsen as a monotherapy followed by combination with Venetoclax in patients with relapsed/refractory myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).
Funding Source: FDA OOPD

Start Date08 May 2024

Sponsor / Collaborator

Montefiore Medical Center

[+2]

NCT05814666 / RecruitingPhase 2

An Open-Label, Phase II, Randomized, Controlled Study of Danvatirsen Plus Pembrolizumab Compared to Pembrolizumab Alone in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Open-label, Phase II, randomized, controlled study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with pembrolizumab alone as first-line treatment of patients with recurrent/metastatic (R/M) HNSCC. Two-thirds of patients will be randomized to receive danvatirsen and pembrolizumab and one-third will be randomized to receive pembrolizumab alone.

Start Date30 May 2023

Sponsor / Collaborator

Flamingo Therapeutics BVStartup

NCT03794544 / CompletedPhase 2

A Phase 2 Open-label, Multicenter, Randomized, Multidrug Platform Study of Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Subjects With Resectable, Early-stage (I [> 2 cm] to IIIA) Non-small Cell Lung Cancer (NeoCOAST)

Study D9108C00002 (NeoCOAST) is a platform study assessing the effectiveness and safety of neoadjuvant durvalumab alone or in combination with novel agents in participants with resectable, early-stage (Stage I [>2cm] to IIIA) non-small cell lung cancer (NSCLC).

Start Date08 Mar 2019

Sponsor / Collaborator

MedImmune LLC

100 Clinical Results associated with Danvatirsen

100 Translational Medicine associated with Danvatirsen

100 Patents (Medical) associated with Danvatirsen

Literatures (Medical) associated with Danvatirsen

01 Mar 2024·Nature medicineQ1 · MEDICINE

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial

Q1 · MEDICINE

Article

Author: Jewsbury, Philip J ; Barrett, J Carl ; Aronson, Boaz ; Shepherd, Frances A ; Cosaert, Jan ; Thomas, Michael ; Johnson, Melissa L ; Awad, Mark M ; Khosla, Sajan ; Morgensztern, Daniel ; Heymach, John V ; Cousin, Sophie ; Russell, Deanna L ; Goss, Glenwood ; Barry, Simon T ; Kim, Sang-We ; Kumar, Rakesh ; Besse, Benjamin ; Moskovitz, Mor T ; Kim, Dong-Wan ; Park, Keunchil ; Pons-Tostivint, Elvire ; Wheatley-Price, Paul ; Dressman, Marlene ; Iyer, Sonia ; Hobson, Rosalind ; Hartl, Sylvia ; Reddy, Avinash ; Dean, Emma ; Cheema, Parneet ; Florescu, Marie ; Conway, James P ; Keddar, Mohamed Reda ; Ambrose, Helen J ; Hochmair, Maximilian J ; Chu, Quincy S C ; Vicente, David ; Forde, Patrick M

Abstract:

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance—which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment—and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)–ceralasertib (ATR kinase inhibitor), durvalumab–olaparib (PARP inhibitor), durvalumab–danvatirsen (STAT3 antisense oligonucleotide) or durvalumab–oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab–ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6–7.4) versus 2.7 (1.8–2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1–20.3) versus 9.4 (7.5–10.6) months. Benefit with durvalumab–ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab–ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab–ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617

01 Nov 2023·Cancer discovery

Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial

Article

Author: Yau, Edwin H ; Sellman, Bret R ; Weder, Walter ; Hamid, Oday ; Kar, Gozde ; Spicer, Jonathan D ; García-Campelo, Rosario ; Soo-Hoo, Yee ; Tan, Tze Heng ; Cascone, Tina ; Mager, Raymond ; McGrath, Lara ; Spira, Alexander I ; Daniel, Davey B ; Rodriguez-Canales, Jaime ; Cheng, Lin-Yang ; Forde, Patrick M ; Grenga, Italia ; Anagnostou, Valsamo ; Surace, Michael ; Zheng, Ying ; Spigel, David R ; Kumar, Rakesh ; Gopalakrishnan, Vancheswaran ; Hussein, Maen ; Mazieres, Julien ; Blando, Jorge ; Oliveira, Julio

Abstract:

Neoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non–small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti–PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms versus durvalumab alone. Safety profiles for the combinations were similar to those of durvalumab alone. Multiplatform immune profiling suggested that improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune cell activation.

Significance::

A neoadjuvant platform trial can rapidly generate clinical and translational data using candidate surrogate endpoints like MPR. In NeoCOAST, patients with resectable NSCLC had improved MPR rates after durvalumab plus oleclumab or monalizumab versus durvalumab alone and tumoral transcriptomic signatures indicative of augmented immune cell activation and function.See related commentary by Cooper and Yu, p. 2306.This article is featured in Selected Articles from This Issue, p. 2293

01 Sep 2023·Clinical cancer research : an official journal of the American Association for Cancer Research

Phase I Study of Acalabrutinib Plus Danvatirsen (AZD9150) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Including Circulating Tumor DNA Biomarker Assessment

Article

Author: Nuttall, Barrett ; Dougherty, Brian ; White, Rafael D. ; Burke, Kathleen ; Mortlock, Andrew ; Reagan, Patrick M. ; Roschewski, Mark ; Flinn, Ian ; Forcina, Alessandra ; de Vos, Sven ; Munugalavadla, Veerendra ; Arkenau, Hendrik-Tobias ; Stetson, Daniel ; Collins, Graham P. ; Udriste, Maria ; Acar, Melih ; Sharma, Shringi ; Saba, Nakhle S. ; Jenkins, David ; Patel, Manish R.

Abstract:

Purpose::

Novel targeted and immunotherapies have improved outcomes in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but toxicities limit widespread use. The selective Bruton tyrosine kinase (BTK) inhibitor acalabrutinib has activity in patients with R/R DLBCL but durable responses are uncommon. STAT3 inhibition has demonstrated clinical activity in DLBCL.

Patients and Methods::

Final results of the phase I study of acalabrutinib plus STAT3 inhibitor (danvatirsen; AZD9150) in patients with R/R DLBCL are reported. Danvatirsen 200 mg intravenous infusion [Days 1, 3, 5 (Cycle 1); weekly infusions starting Day 8, Cycle 1] was administered in combination with oral acalabrutinib 100 mg twice daily until progressive disease (PD) or unacceptable toxicity. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy, pharmacokinetics, and immunogenicity.

Results::

Seventeen patients received combination treatment. One dose-limiting toxicity (Grade 3 liver transaminase) occurred in 1 patient. The most common reason for treatment discontinuation was PD (65%). In evaluable patients (n = 17), objective response rate was 24%; median duration of response was 1.9 months. All responders with available DLBCL cell-of-origin data were either activated B-cell or nongerminal center B-cell like subtype. Genetic subtype did not correlate with response. Baseline and longitudinal plasma cell-free DNA (cfDNA) concentrations were mostly higher in nonresponding patients. cfDNA changes were generally concordant with imaging. Pretreatment circulating B-cell levels were higher in responders versus nonresponders.

Conclusions::

Targeting both STAT3 and BTK in combination is safe and tolerable but efficacy is limited in R/R DLBCL. Results support evaluation of circulating tumor DNA as a biomarker for clinical response.

News (Medical) associated with Danvatirsen

04 Dec 2024

·www.prnewswire.com

Flamingo Therapeutics Announces Poster Presentation on AML Phase 1 IIT Study at ASH 2024

LEUVEN, Belgium and STRASBOURG, France and PHILADELPHIA, Dec. 4, 2024 /PRNewswire/ -- Flamingo Therapeutics ("Flamingo") today announced that an abstract has been selected for presentation at the 66th Annual ASH Annual Meeting and Exposition, being held in San Diego, CA from December 7-9, 2024. The abstract, selected for a poster presentation, is a Trials-in-Progress presentation of a Phase 1 investigator-initiated study of danvatirsen monotherapy followed by danvatirsen combination with venetoclax in relapsed/refractory AML and intermediate/high risk MDS (NCT05986240). The study is being conducted at Albert Einstein / Montefiore Medical Center in New York City and MD Anderson Cancer Center in Houston. Poster presentation details are as follows: Title: "A Phase 1 Study Investigating the Safety and Efficacy of Danvatirsen As Monotherapy Followed by Combination with Venetoclax in Patients with Relapsed/Refractory MDS and AML" Session Date: Monday, December 9, 2024 Presenting Author: Dr. Aditi Shastri For more information, please visit the ASH 2024 website. About Flamingo Therapeutics Flamingo is pioneering RNA-targeted therapies for oncology with a clinical-stage pipeline targeting undruggable transcription factors and long non-coding RNAs. Flamingo has an alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors including Abrdn (formerly funds managed by Tekla Capital Management LLC), Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Eurazeo - Kurma Partners, Perceptive Advisors, PMV, Pontifax, Sphera, and VIB. Flamingo has initiated a Phase II trial 'PEMDA-HN' evaluating the STAT3 targeting agent danvatirsen, in combination with pembrolizumab, in patients with head and neck squamous cell carcinoma (HNSCC). A Phase I investigator initiated trial study has also been initiated evaluating danvatirsen as a monotherapy and in combination with venetoclax in AML/MDS patients. For more information on Flamingo, please visit: PEMDA-HN (head and neck cancer) on clinicaltrials.gov: Danvatirsen monotherapy followed by combination with venetoclax in relapsed/ refractory AML and MDS on clincaltrials.gov: Please engage with us on LinkedIn: . Flamingo Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Flamingo Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 1Phase 2AACRsiRNA

29 Aug 2024

·www.prnewswire.com

Flamingo Therapeutics Announces Participation in Upcoming Investor Conferences

LEUVEN, Belgium and STRASBOURG, France and PHILADELPHIA, Aug. 29, 2024 /PRNewswire/ -- Flamingo Therapeutics ("Flamingo") announced today its participation in the following upcoming investor conferences: Wells Fargo Annual Healthcare Conference, September 4-6, 2024, Boston, MA PA Life Sciences Future Conference, September 18-19, 2024, Philadelphia, PA 8th Annual Chardan Genetic Medicines Conference, September 30-October 1, 2024, NY 4th Annual Needham Private Biotech Company Virtual 1x1 Forum, October 8-9, 2024 During these events, Company management will participate in one-on-one meetings with investors. About Flamingo Therapeutics Flamingo is pioneering RNA-targeted therapies for oncology with a clinical-stage pipeline targeting undruggable transcription factors and long non-coding RNAs. Flamingo has an alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors including Abrdn (formerly funds managed by Tekla Capital Management LLC), Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Eurazeo - Kurma Partners, Perceptive Advisors, PMV, Pontifax, Sphera, and VIB. Flamingo has initiated a Phase II trial 'PEMDA-HN' evaluating the STAT3 targeting agent danvatirsen, in combination with pembrolizumab, in patients with head and neck squamous cell carcinoma (HNSCC). A Phase I investigator initiated trial study has also been initiated evaluating danvatirsen as a monotherapy and in combination with venetoclax in AML/MDS patients. For more information on Flamingo, please visit: PEMDA-HN (head and neck cancer) on clinicaltrials.gov: Danvatirsen monotherapy followed by combination with venetoclax in relapsed/ refractory AML and MDS on clincaltrials.gov: Please engage with us on LinkedIn: . Flamingo Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Flamingo Therapeutics

Phase 1Phase 2siRNA

10 Jun 2024

·www.prnewswire.com

Flamingo Therapeutics Announces Poster Presentation at EACR 2024 Congress on FLM-7523 (FTX-001), a First-in-Class Inhibitor of the Long Non-Coding RNA MALAT1

LEUVEN, Belgium and STRASBOURG, France and PHILADELPHIA , June 10, 2024 /PRNewswire/ -- Flamingo Therapeutics ("Flamingo") today announced a poster presentation on FLM-7523 (also referred to as FTX-001) at the Annual Congress of the European Association for Cancer Research (EACR) 2024 Congress, being held in Rotterdam, Netherlands from June 10-13, 2024. Flamingo will present preclinical results highlighting the candidate selection and characterization of FLM-7523, a novel oligonucleotide targeting MALAT1 for the treatment of cancer. Flamingo has advanced FLM-7523 through Phase 1 enabling preclinical activities and is planning for a First-in-Human trial in solid tumors. EACR poster details are as follows: Abstract#: EACR2024-0240 Title: "Preclinical development of FTX-001: First-in-class inhibitor of the long non-coding RNA MALAT1" Session Title: Posters: Experimental/Molecular Therapeutics, Pharmacogenomics Session Date and Time: June 11, 2024, from 11:00 to 20:15 Presenting Author: Dr. Marie-Aline Neveu Abstracts related to the EACR meeting will be published online in a supplement to the FEBS journal, Molecular Oncology, the Congress App and the Congress Website. For more information, please visit the EACR 2024 website. About Flamingo Therapeutics Flamingo is pioneering RNA-targeted therapies for oncology with a clinical-stage pipeline targeting undruggable transcription factors and long non-coding RNAs. Flamingo has an alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors including Abrdn (formerly funds managed by Tekla Capital Management LLC), Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Eurazeo - Kurma Partners, Perceptive Advisors, PMV, Pontifax, Sphera, and VIB. Flamingo has initiated a Phase II trial 'PEMDA-HN' evaluating the STAT3 targeting agent danvatirsen, in combination with pembrolizumab, in patients with head and neck squamous cell carcinoma (HNSCC). A Phase I investigator-initiated trial study has also been initiated evaluating danvatirsen as a monotherapy and in combination with venetoclax in AML/MDS patients. For more information on Flamingo, please visit: PEMDA-HN (head and neck cancer) on clinicaltrials.gov: Danvatirsen monotherapy followed by combination with venetoclax in relapsed/ refractory AML and MDS on clincaltrials.gov: Please engage with us on LinkedIn: . Flamingo Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Flamingo Therapeutics

Phase 1Phase 2AACROligonucleotide

100 Deals associated with Danvatirsen

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14825

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Squamous Cell Carcinoma of Head and Neck	Phase 2	US	Flamingo Therapeutics BVStartup	30 May 2023
Squamous Cell Carcinoma of Head and Neck	Phase 2	KR	Flamingo Therapeutics BVStartup	30 May 2023
Squamous Cell Carcinoma of Head and Neck	Phase 2	GB	Flamingo Therapeutics BVStartup	30 May 2023
Advanced Colorectal Adenocarcinoma	Phase 2	US	AstraZeneca PLC	02 Mar 2017
Advanced Lung Non-Small Cell Carcinoma	Phase 2	US	AstraZeneca PLC	02 Mar 2017
Colorectal Cancer, Hereditary Nonpolyposis, Type 1	Phase 2	US	AstraZeneca PLC	02 Mar 2017
Microsatellite instability-high colorectal cancer	Phase 2	US	AstraZeneca PLC	02 Mar 2017
Pancreatic Cancer	Phase 2	US	AstraZeneca PLC	02 Mar 2017
Refractory Colorectal Carcinoma	Phase 2	US	AstraZeneca PLC	02 Mar 2017
Refractory Lung Carcinoma	Phase 2	US	AstraZeneca PLC	02 Mar 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03794544 (AACR2022) Manual	Phase 2	Non-Small Cell Lung Cancer Neoadjuvant	84	Durvalumab	xbcusgqsxl(gzbtjuvspr) = szughtfniv dcashfidxt (hpmpwhhgkc, 2.4 - 29.2) View more	Positive	15 Jun 2022
NCT03794544 (AACR2022) Manual	Phase 2	Non-Small Cell Lung Cancer Neoadjuvant	84	Durvalumab+Oleclumab	xbcusgqsxl(gzbtjuvspr) = kglmoukyow dcashfidxt (hpmpwhhgkc, 5.4 - 41.9) View more	Positive	15 Jun 2022
NCT03421353 (AACR2020)	Phase 1	HR-positive/HER2-low Solid Tumors	76	Danvatirsen 200 mg IV QW	blrxhazfpy(iqhxzgfmpz) = umawlbotxg nlkubpjdpp (qehcnyvjmk ) View more	-	15 Aug 2020
NCT03421353 (AACR2020)	Phase 1	HR-positive/HER2-low Solid Tumors	76	Danvatirsen 400 mg IV Q2W	blrxhazfpy(iqhxzgfmpz) = zmpdjayewo nlkubpjdpp (qehcnyvjmk ) View more	-	15 Aug 2020
NCT01563302 (Pubmed \| J Immunother Cancer) Manual	Phase 1	Lymphoma	30	AZD9150	dkmwgslcef(fwmawdxikb) = ikrycryxda ywvprunfku (itdwqefhdd ) View more	Positive	16 Nov 2018
NCT02417753 (CTgov)	Phase 2	Ovarian Cancer \| Malignant ascites \| Gastrointestinal Neoplasms	1	AZD9150	fdhwckrzbu(mpcpwkkvxr) = ruxvpjjmke vngyfebjwt (iujfttkxtg, hfcatnqqge - dbthpxqyrx) View more	-	15 May 2017
NCT01563302 (ASCO2013)	Phase 1	Advanced cancer	15	ISIS 481464	tlestkwfsi(cxcfvejemr) = xeblxernso vxvmxnijnn (tdlxclrysb )	-	20 May 2013

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