CARRIE: A randomized, double-blind, placebo-controlled phase II study of istiratumab (MM-141) plus nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine in front-line metastatic pancreatic cancer

Ko, Andrew H.; Cubillo, Antonio; Kundranda, Madappa N.; Zafar, Syed F.; Meiri, Eyal; Bendell, J. C.; Alguel, Hana; Herrero, F. Rivera; Ahn, E.; Watkins, D.; Pelzer, Uwe; Charu, V.; Downing, W.; Wang, B.; Kuesters, Geoffrey; Pipas, J. Marc; Santillana, Sergio; Askoxylakis, Vasileios

doi:10.1093/annonc/mdy424.031

Cited by 8 publications

(6 citation statements)

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“…88 patients were enrolled; the study failed to show mOS or mPFS improvement in favour of the investigational arm (mOS:8.9 months, mPFS:3.6 months) as compared to the control arm (mOS:11.7 months, mPFS:7.3 months). Similar results were reported for the group of patients with high free IGF-1 serum levels and Heregulin-positive tumours [52].…”

Section: Igfr Inhibitorssupporting

confidence: 88%

New therapeutic targets in pancreatic cancer

Lai

Puzzoni

Ziranu

et al. 2019

Cancer Treatment Reviews

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Igfr Inhibitorssupporting

confidence: 88%

New therapeutic targets in pancreatic cancer

Lai

Puzzoni

Ziranu

et al. 2019

Cancer Treatment Reviews

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“…Based on these results, a randomized, double-blind, phase II study was conducted to compare the efficacy of the combination of MM-141 plus nab-paclitaxel and gemcitabine with that of nab-paclitaxel and gemcitabine alone in metastatic pancreatic cancer patients with high serum levels of free IGF-1 (CARRIE; ClinicalTrials.gov: NCT02399137). The results showed that this combination was not more effective than nab-paclitaxel and gemcitabine alone in enrolled patients 135 …”

Section: Main Textmentioning

confidence: 92%

Single-Chain Variable Fragment-Based Bispecific Antibodies: Hitting Two Targets with One Sophisticated Arrow

Ahamadi-Fesharaki

Fateh

Vaziri

et al. 2019

Molecular Therapy - Oncolytics

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Despite the success of monoclonal antibodies (mAbs) to treat some disorders, the monospecific molecular entity of mAbs as well as the presence of multiple factors and pathways involved in the pathogenesis of disorders, such as various malignancies, infectious diseases, and autoimmune disorders, and resistance to therapy have restricted the therapeutic efficacy of mAbs in clinical use. Bispecific antibodies (bsAbs), by concurrently recognizing two targets, can partly circumvent these problems. Serial killing of tumor cells by bsAb-redirected T cells, simultaneous blocking of two antigens involved in the HIV-1 infection, and concurrent targeting of the activating and inhibitory receptors on B cells to modulate autoimmunity are part of the capabilities of bsAbs. After designing and developing a large number of bsAbs for years, catumaxomab, a full-length bsAb targeting EpCAM and CD3, was approved in 2009 to treat EpCAM-positive carcinomas besides blinatumomab, a bispecific T cell engager antibody targeting CD19 and CD3, which was approved in 2014 to treat relapsed or refractory acute lymphoblastic leukemia. Furthermore, approximately 60 bsAbs are under investigation in clinical trials. The current review aims at portraying different formats of the single-chain variable fragment (scFv)-based bsAbs and shedding light on the scFv-based bsAbs in preclinical development, different phases of clinical trials, and the market.

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“…The development of the bispecific HER3/IGF-1R-directed MoAb istiratumab (MM-141) was discontinued by the Sponsor following the negative results of the phase II CARRIE trial, as its addition to first-line nab-paclitaxel and gemcitabine did not show a clinical benefit in patients with metastatic pancreatic cancer with high IGF-1 serum levels. 43 …”

Section: Beyond Her3-directed Moab: Bispecific Antibodiesmentioning

confidence: 99%