An Open-Label, Multicenter, Phase Ib Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumor Activity Of RO7122290, A Fibroblast Activation Protein-A (FAP) Targeted 4-1BB Ligand (CD137L), In Combination With Cibisatamab With Obinutuzumab Pre-Treatment, In Participants With Previously Treated, Metastatic, Microsatellite-stable Colorectal Adenocarcinoma With High CEACAM5 Expression

This is an open-label, multicenter, Phase Ib study to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) in the weekly (QW) and/or every 3 weeks (Q3W) regimens, safety, tolerability, PK, immunogenicity, PD profile and to evaluate preliminary anti-tumor activity of RO7122290 in combination with cibisatamab Q3W after pretreatment with obinutuzumab, in participants with previously treated metastatic, microsatellite-stable colorectal adenocarcinoma with high CEACAM5 expression

Start Date14 Jul 2021

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

NCT03866239 / TerminatedPhase 1

A Phase Ib, Multicenter, Open-Label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Cibisatamab in Combination With Atezolizumab After Pretreatment With Obinutuzumab in Patients With Previously Treated Metastatic, Microsatellite-Stable Colorectal Adenocarcinoma With High CEACAM5 Expression

CO40939 is a Phase Ib, open-label, multicenter, single-arm study designed to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of cibisatamab in combination with atezolizumab administered after pretreatment with obinutuzumab in patients with Stage IV microsatellite stable (MSS) metastatic colorectal cancer (mCRC) whose tumors have high carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression and who have progressed on two or more chemotherapy regimens. The study is composed of a safety run-in and an exploratory part.

Start Date07 May 2019

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

NCT03337698 / Active, not recruitingPhase 1/2

A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations In Patients With Metastatic Non-Small Cell Lung Cancer (Morpheus-Lung)

This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (NSCLC).
Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of participants with tumor PD-L1 expression who have received no prior systemic therapy for metastatic NSCLC, and Cohort 2 will consist of participants who experienced disease progression during or following treatment with a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor, given in combination as one line of therapy or as two separate lines of therapy, regardless of PD-L1 expression. In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). Participants who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen (Stage 2).

Start Date02 Jan 2018

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

100 Clinical Results associated with Cibisatamab

100 Translational Medicine associated with Cibisatamab

100 Patents (Medical) associated with Cibisatamab

508

Literatures (Medical) associated with Cibisatamab

01 Oct 2024·Theriogenology

A study on methods for preimplantation genetic testing (PGT) on in vivo- and in vitro-produced equine embryos, with emphasis on embryonic sex determination

Article

Author: Castaneda, Caitlin ; Love, Charles C ; Ramírez-Agámez, Luisa ; Raudsepp, Terje ; Hernández-Avilés, Camilo ; Grahn, Robert A

Two methods for preimplantation genetic testing (PGT) have been described for equine embryos: trophoblast cell biopsy (TCB) or blastocoele fluid aspiration (BFA). While TCB is widely applied for both in vivo- and in vitro-produced embryos, BFA has been mostly utilized for in vivo-produced embryos. Alternative methods for PGT, including analysis of cell-free DNA (CFD) in the medium where in vitro-produced embryos are cultured, have been reported in humans but not for equine embryos. In Experiment 1, in vivo- (n = 10) and in vitro-produced (n = 13) equine embryos were subjected to BFA, cultured for 24 h, then subjected to TCB, and cultured for additional 24 h. No detrimental effect on embryonic diameter or re-expansion rates was observed for either embryo group (P > 0.05). In Experiment 2, the concordance (i.e., agreement on detecting the same embryonic sex using two techniques) among BFA, TCB, and the whole embryo (Whole) was studied by detecting the sex-determining region Y (SRY) or testis-specific y-encoded protein 1 (TSPY) (Y-chromosome), and androgen receptor (AR; X-chromosome) genes using PCR. Overall, a higher concordance for detecting embryonic sex was observed among techniques for in vivo-produced embryos (67-100 %; n = 14 embryos) than for in vitro-produced embryos (31-92 %; n = 13 embryos). The concordance between sample types increased when utilizing TSPY (77-100 %) instead of SRY (31-100 %) as target gene. In Experiment 3, CFD analysis was performed on in vitro-produced embryos to determine embryonic sex via PCR (SRY [Y-chromosome] and amelogenin - AMEL [X- and Y-chromosomes]). Overall, CFD was detected in all medium samples, and the concordance between CFD sample and the whole embryo was 60 % when utilizing SRY and AMEL genes. In conclusion, equine embryos can be subjected to two biopsy procedures (24 h apart) without apparent detrimental effects on embryonic size. For in vivo-, but not for in vitro-produced equine embryos, BFA can be considered a potential alternative to TCB for PGT. Finally, CFD can be further explored as a non-invasive method for PGT in in vitro produced equine embryos.

02 Jul 2024·Molecular Cancer Therapeutics

Optimizing the Design and Geometry of T Cell–Engaging Bispecific Antibodies Targeting CEA in Colorectal Cancer

Article

Author: Thoma, Marina ; Zangger, Nathan ; Pfister, Stefanie K. ; Pellegrino, Christian ; Nideroest, Larissa ; Peissert, Frederik ; De Luca, Roberto ; Oxenius, Annette ; Neri, Dario ; Elsayed, Abdullah ; Rotta, Giulia ; Manz, Markus G. ; Halin, Cornelia ; Plüss, Louis ; Dakhel Plaza, Sheila ; Puca, Emanuele

AbstractMetastatic colorectal cancer remains a leading cause of cancer-related deaths, with a 5-year survival rate of only 15%. T cell–engaging bispecific antibodies (TCBs) represent a class of biopharmaceuticals that redirect cytotoxic T cells toward tumor cells, thereby turning immunologically “cold” tumors into “hot” ones. The carcinoembryonic antigen (CEA) is an attractive tumor-associated antigen that is overexpressed in more than 98% of patients with colorectal cancer. In this study, we report the comparison of four different TCB formats employing the antibodies F4 (targeting human CEA) and 2C11 (targeting mouse CD3ε). These formats include both antibody fragment–based and IgG-based constructs, with either one or two binding specificities of the respective antibodies. The 2 + 1 arrangement, using an anti-CEA single-chain diabody fused to an anti-CD3 single-chain variable fragment, emerged as the most potent design, showing tumor killing at subnanomolar concentrations across three different CEA+ cell lines. The in vitro activity was three times greater in C57BL/6 mouse colon adenocarcinoma cells (MC38) expressing high levels of CEA compared with those expressing low levels, highlighting the impact of CEA density in this assay. The optimal TCB candidate was tested in two different immunocompetent mouse models of colorectal cancer and showed tumor growth retardation. Ex vivo analysis of tumor infiltrates showed an increase in CD4+ and CD8+ T cells upon TCB treatment. This study suggests that bivalent tumor targeting, monovalent T-cell targeting, and a short spatial separation are promising characteristics for CEA-targeting TCBs.

01 Jul 2024·Journal of Trauma and Acute Care Surgery

Is barbed better? Evaluation of triclosan-coated barbed suture on wound complications following emergency laparotomy

Article

Author: Dilday, Joshua ; Park, Stephen ; Matsushima, Kazuhide ; Gallagher, Shea ; Schellenberg, Morgan ; Martin, Matthew J ; McGillen, Patrick ; Lee, Heewon ; Inaba, Kenji

INTRODUCTIONEmergent laparotomy is associated with significant wound complications including surgical site infections (SSIs) and fascial dehiscence. Triclosan-coated barbed (TCB) suture for fascial closure has been shown to reduce local complications but primarily in elective settings. We sought to evaluate the effect of TCB emergency laparotomy fascial closure on major wound complications.METHODSAdult patients undergoing emergency laparotomy were prospectively evaluated over 1 year. Patients were grouped into TCB versus polydioxanone (PDS) for fascial closure. Subanalysis was performed on patients undergoing single-stage laparotomy. Primary outcomes were SSI and fascial dehiscence. Multivariate analysis identified independent factors associated with SSI and fascial dehiscence.RESULTSOf the 206 laparotomies, 73 (35%) were closed with TCB, and 133 (65%) were closed with PDS. Trauma was the reason for laparotomy in 73% of cases; damage-control laparotomy was performed in 27% of cases. The overall rate of SSI and fascial dehiscence was 18% and 10%, respectively. Operative strategy was similar between groups, including damage-control laparotomy, wound vac use, skin closure, and blood products. Surgical site infection events trended lower with TCB versus PDS closure (11% vs. 21%, p = 0.07), and fascial dehiscence was significantly lower with TCB versus PDS (4% vs. 14%, p < 0.05). Subanalysis of trauma and nontrauma cases showed no difference in SSI or fascial dehiscence. Multivariable analysis found that TCB decreased the likelihood of fascial dehiscence (odds ratio, 0.07; p < 0.05) following emergency laparotomy. Increased odds of fascial dehiscence were seen in damage-control laparotomy (odds ratio, 3.1; p < 0.05).CONCLUSIONEmergency laparotomy fascial closure with TCB showed significantly decreased rates of fascial dehiscence compared with closure with PDS and a strong trend toward lower SSI events. Triclosan-coated barbed suture was independently associated with decreased fascial dehiscence rates after emergency laparotomy.LEVEL OF EVIDENCETherapeutic/Care Management; Level III.

News (Medical) associated with Cibisatamab

20 Mar 2024

·www.globenewswire.com

CytomX Therapeutics Announces Milestone Achievement in PROBODY® T-Cell Engaging Bispecific (TCB) Collaboration with Astellas

- Initiation of GLP toxicology study for the first clinical candidate in the collaboration triggers a $5 million milestone payment to CytomX - - Program is one of several ongoing collaboration projects in broad CytomX-Astellas alliance on T-cell engaging bispecifics - - CytomX retains option for US co-commercialization and economic rights for certain programs - March 18, 2024 -- CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated, localized biologics, today announced that the first clinical candidate in its TCB agreement with Astellas has entered into GLP toxicology studies which triggers a $5 million payment to CytomX. The clinical candidate is the first PROBODY® TCB molecule under this alliance to progress into a GLP toxicology study. CytomX and Astellas are also collaborating on additional conditionally activated TCB programs with CytomX eligible to receive future preclinical, clinical and commercial milestones. CytomX retains a cost share and co-commercialization option on a select number of targets. “We are excited by the continued momentum towards a potential future IND for the first PROBODY® TCB clinical candidate in our collaboration with Astellas, and we continue to partner with Astellas on multiple preclinical programs. The progress with this collaboration highlights the benefits of our strategy to create value through both wholly-owned and partnered programs, as well as the potential of our expanding pipeline of PROBODY T-cell engagers which are designed to localize T-cell activity to the tumor microenvironment,” said Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX Therapeutics. CytomX is a clinical-stage, oncology-focused biopharmaceutical company focused on developing novel conditionally activated biologics designed to be localized to the tumor microenvironment. By pioneering a novel pipeline of localized biologics, powered by its PROBODY® therapeutic platform, CytomX’s vision is to create safer, more effective therapies for the treatment of cancer. CytomX’s robust and differentiated pipeline comprises therapeutic candidates across multiple treatment modalities including antibody-drug conjugates (“ADCs”), T-cell engagers, and immune modulators such as cytokines. CytomX’s clinical-stage pipeline includes CX-904, CX-2051 and CX-801. CX-904 is a conditionally activated T-cell-engaging antibody targeting the epidermal growth factor receptor (EGFR) on tumor cells and the CD3 receptor on T cells and partnered with Amgen in a global co-development alliance. CX-2051 is a conditionally activated ADC directed toward epithelial cell adhesion molecule, EpCAM, with potential applicability across multiple EpCAM-expressing epithelial cancers. CX-801 is an interferon alpha-2b PROBODY® cytokine with broad potential applicability in traditionally immuno-oncology sensitive as well as insensitive (cold) tumors. CytomX has established strategic collaborations with multiple leaders in oncology, including Amgen, Astellas, Bristol Myers Squibb, Regeneron and Moderna. For more information about CytomX and how it is working to make conditionally activated treatments the new standard-of-care in the fight against cancer, visit www.cytomx.com and follow us on LinkedIn and X (formerly Twitter). The content above comes from the network. if any infringement, please contact us to modify.

License out/in

19 Oct 2023

·www.fiercebiotech.com

Roche drops oral eye disease drug after completing phase 2, pulls back from solid tumor bispecific

Roche removed schizophrenia candidate ralmitaront from its midphase pipeline. Roche’s vision of developing an oral diabetic retinopathy treatment has taken a hit, with the drugmaker stopping development of vicasinabin after completing phase 2. The CB2 agonist was discarded (PDF) as part of a cull that also saw Roche pull back from its CEAxCD3 bispecific candidate cibisatamab. Vicasinabin, also known as RG7774, entered phase 2 in 2020. Roche pitched the candidate as a potential oral alternative to existing invasive treatments, such as injections into the eye, for a condition that leads to vision loss and blindness in some people with diabetes. However, the clinical trial, which finished in July, failed to persuade Roche to keep investing in the candidate. The action eliminates one of the leading oral contenders in diabetic retinopathy. Ocuphire Pharma has an oral candidate, APX3330, that has cleared phase 2. Bayer, InflammX and Rezolute also have oral, clinical-phase assets. Other companies, notably Boehringer Ingelheim, have swung at the indication and missed. Roche dropped vicasinabin from its pipeline as part of a third quarter cull that also affected cibisatamab, a bispecific designed to bind to CD3 on T cells and CEA on cancer cells. Multiple companies have zeroed in on CEA as an attractive solid tumor drug target. Roche started a phase 1 trial of an older CEAxCD3 bispecific, RO6958688, in 2014 and followed up by taking cibisatamab into the clinic in 2019. The trial evaluated cibisatamab, also known as RG7802, in combination with Roche’s checkpoint inhibitor Tecentriq in colorectal cancer patients. Now, Roche has removed RG7802 in solid tumors from its phase 1 pipeline. The drugmaker continues to assess RG7802 in combination with RO7122290, a bispecific antibody-like fusion protein that simultaneously targets 4-1BB and FAP, in colorectal cancer. Asked by Fierce Biotech about the pipeline changes on a conference call with the media this morning, Teresa Graham, CEO of Roche Pharmaceuticals, said: “I think these are both very early-stage assets that currently sit in our research and early development organizations.” “We've seen encouraging early data that would lead us to believe that further study is necessary or warranted,” Graham added. “So I would say stay tuned, and hopefully at an upcoming medical conference we'll have more data that we can share.” Roche also removed the schizophrenia candidate ralmitaront from its midphase pipeline. The company terminated a phase 2 trial of the asset earlier this year after an interim analysis found it was unlikely to meet the primary endpoint. Roche terminated another trial of the molecule last year.

Phase 2Phase 1Clinical Trial Failure

19 Oct 2023

·endpts.com

Roche makes four pipeline changes on back of trial failures, but sees path ahead for three therapies

Roche is reworking its plans for a quartet of clinical programs spanning different therapeutic areas and stages of development, but it may not be the end of the road for most of the drugs affected. The Swiss drugmaker revealed it was dropping its Phase I solid tumor trial for cibisatamab, as well as Phase II programs for ralmitaront in schizophrenia and vicasinabin in diabetic retinopathy, according to a pipeline document released as part of Thursday’s third-quarter earnings update. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

Phase 2Phase 1Clinical Trial FailureClinical Trial Termination

100 Deals associated with Cibisatamab

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Discovery	NL	F. Hoffmann-La Roche Ltd.	21 Apr 2021
Colorectal Cancer	Discovery	GB	F. Hoffmann-La Roche Ltd.	21 Apr 2021
Non-Small Cell Lung Cancer	Discovery	IL	F. Hoffmann-La Roche Ltd.	02 Jan 2018
Non-Small Cell Lung Cancer	Discovery	ES	F. Hoffmann-La Roche Ltd.	02 Jan 2018
Non-Small Cell Lung Cancer	Discovery	FR	F. Hoffmann-La Roche Ltd.	02 Jan 2018
Non-Small Cell Lung Cancer	Discovery	GB	F. Hoffmann-La Roche Ltd.	02 Jan 2018
Non-Small Cell Lung Cancer	Discovery	AU	F. Hoffmann-La Roche Ltd.	02 Jan 2018
Non-Small Cell Lung Cancer	Discovery	CN	F. Hoffmann-La Roche Ltd.	02 Jan 2018
Non-Small Cell Lung Cancer	Discovery	KR	F. Hoffmann-La Roche Ltd.	02 Jan 2018
Non-Small Cell Lung Cancer	Discovery	US	F. Hoffmann-La Roche Ltd.	02 Jan 2018

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02324257 (ESMO2017) Manual	Phase 1	Metastatic colon cancer CEA Positive	45	RG7802 (CRC and At doses ≥ 60 mg)	(edwudaqamq) = In S1 (out of 59 pts > 40 mg), IRRs (24%) and diarrhea (7%). fvnysljjbd (nogxaigdwy ) View more	Positive	11 Sep 2017
				Atezolizumab+RG7802 (CRC and At doses ≥ 60 mg)
NCT02324257 \| NCT02650713 (ASCO2017)	Phase 1	Metastatic Colorectal Carcinoma	-	CEA-CD3 TCB	(oqnrahkucx) = qdgfkzisbm nyrlzephbn (zirbogkcil ) View more	-	30 May 2017
				Atezolizumab	(oqnrahkucx) = vnfemnwcof nyrlzephbn (zirbogkcil )

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