- |||||||||| depatuxizumab (ABT-806) / AbbVie, Life Science Pharma, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Clinical, Journal: Most clinical anti-EGFR antibodies do not neutralize both wtEGFR and EGFRvIII activation in glioma. (Pubmed Central) - Apr 28, 2021
We discovered a previously unknown major resistance mechanism in glioma in that most EGFR domain III-targeting antibodies do not neutralize EGFRvIII. The superior in vitro and in vivo anti-tumor activity of panitumumab support further clinical testing of this antibody against EGFRvIII-stratified glioma.
- |||||||||| CDX-3379 / Celldex
Trial completion, Trial completion date, Combination therapy, Metastases: A Study of CDX-3379 and Cetuximab and in Patients With Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - Apr 28, 2021
P2, N=30, Completed,
Preventive intervention to maintain general condition without simultaneously exceeding level 2 of PS and mGPS might be important for improving treatment outcomes of nivolumab. Active, not recruiting --> Completed | Trial completion date: Aug 2021 --> Dec 2020
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono, Opdivo (nivolumab) / Ono Pharma, BMS
Clinical, Review, Journal: Monoclonal antibody extravasations: Two case reports and literature review. (Pubmed Central) - Apr 27, 2021
We reviewed published information about MoAb extravasations. In conclusion, not all MoAb should be classified in the same category when extravasated and special precautions are warranted with conjugated MoAb and bevacizumab.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
[VIRTUAL] Encorafenib plus Cetuximab, with or without Binimetinib, for BRAF V600EPositive Metastatic Colorectal Cancer: Relationship Between Carcinoembryonic Antigen and Clinical Outcomes from BEACON CRC () - Apr 26, 2021 - Abstract #HOPA2021HOPA_135;
P3
Among patients receiving the EBC or EC regimen, lower baseline CEA was associated with longer OS; among patients with the highest baseline CEA, reduction in CEA with treatment was associated with improved OS. The baseline CEA and early on-treatment changes in CEA and CA19-9 levels may potentially identify a subgroup of patients with a numerically greater increase in survival and improved clinical outcomes with targeted therapy for metastatic CRC with BRAF V600E mutation.
- |||||||||| [VIRTUAL] Effect of prior bevacizumab treatment in BRAF V600E-mutant metastatic colorectal cancer: Overall survival with encorafenib + cetuximab +/- binimetinib in BEACON CRC () - Apr 26, 2021 - Abstract #ESMOGI2021ESMO_GI_100;
P3
The trial evaluated encorafenib plus cetuximab with or without binimetinib (triplet or doublet, respectively) versus investigators choice of irinotecan or FOLFIRI plus cetuximab (control)...Additional analyses exploring the potential impact of prior bevacizumab use on encorafenib plus cetuximab with or without binimetinib treatment will be presented. Conclusions This exploratory post hoc analysis evaluates OS in patients from BEACON CRC treated with encorafenib plus cetuximab with or without binimetinib to investigate the potential effects of prior bevacizumab treatment on subsequent regimens for patients with BRAF V600E-mutant mCRC.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
[VIRTUAL] ANCHOR CRC: Results from a single-arm, phase 2 study of encorafenib, binimetinib plus cetuximab in previously untreated BRAF V600E–mutant metastatic colorectal cancer () - Apr 26, 2021 - Abstract #ESMOGI2021ESMO_GI_99;
P2
Despite the high-risk features of the population enrolled in this study, almost half of the patients responded and most had disease control, with a median PFS of 5.8 months and a median OS of 17.2 months. The safety profile was acceptable and toxicities remained manageable.
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono, Zelboraf (vemurafenib) / Roche
[VIRTUAL] 5-FU/LV + cetuximab + vemurafenib as maintenance therapy for BRAF-mutant (BRAFmut) metastatic colorectal cancer: Efficacy, safety, and exploratory biomarker findings from Cohort 1 of the MODUL trial () - Apr 26, 2021 - Abstract #ESMOGI2021ESMO_GI_98;
P2
Methods Control treatment was fluoropyrimidine [FP]/bevacizumab (1600 2400 mg/m 2 5-FU 46-h IV infusion d1 q2w; LV 400 mg/m 2 2-h infusion d1 q2w; or 1000 mg/m 2 bid capecitabine orally d1 14 q3w; bevacizumab 5 mg/kg 15 30-min IV infusion d1 q2w)...Exploratory biomarker findings revealed that selective pressure of the treatment arm leads to acquired mutations that reactivate and converge in the MAPK pathway as drivers of resistance to cetuximab + vemurafenib. Further mutation analyses need to be performed to confirm and identify other mechanisms of resistance to cetuximab + vemurafenib in patients with BRAF mut mCRC that might inform future combination strategies.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono
[VIRTUAL] Final overall survival for the phase 3 KN177 study: Pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer () - Apr 26, 2021 - Abstract #ESMOGI2021ESMO_GI_93;
P3
Methods A total of 307 patients with MSI-H/dMMR mCRC and ECOG PS 0 or 1 were randomized 1:1 to 1L pembrolizumab 200 mg Q3W for up to 2y or investigator s choice of mFOLFOX6 or FOLFIRI Q2W bevacizumab or cetuximab...Conclusions As 1L therapy for patients with MSI-H/dMMR mCRC, pembrolizumab vs chemotherapy provides statistically superior PFS with fewer TRAEs, and is associated with a trend toward reduced mortality that did not meet statistical significance likely due to the high crossover rate from chemotherapy to anti-PD1/PD-L1 therapies. Together these data confirm pembrolizumab as a new standard-of-care in the 1L for patients with MSI-H/dMMR mCRC.
- |||||||||| Lonsurf (trifluridine/tipiracil) / Servier, Otsuka, TTY Biopharm, Erbitux (cetuximab) / Eli Lilly, EMD Serono
[VIRTUAL] Gene alterations in ctDNA related to the resistance mechanism of anti-EGFR antibodies and clinical efficacy outcomes of anti-EGFR antibody rechallenge plus trifluridine/tipiracil in metastatic colorectal cancer patients in WJOG8916G trial () - Apr 26, 2021 - Abstract #ESMOGI2021ESMO_GI_80;
Background We conducted a phase II trial (WJOG8916G) to evaluate the efficacy and safety of the combination of trifluridine/tipiracil and cetuximab rechallenge in patients (pts) with metastatic colorectal cancer (mCRC) refractory to anti-epidermal growth factor receptor (EGFR) antibodies...Methods Major eligibility criteria were the following: histologically proven unresectable mCRC; RAS (KRAS and NRAS) exon 2,3,4 wild-type in archived tumor tissues; refractory or intolerance to fluoropyrimidines, oxaliplatin, irinotecan, and anti-angiogenic agents; refractory to anti-EGFR antibodies; and ECOG PS 0 1...Conclusions RAS, BRAF, and PIK3CA muts in ctDNA were associated with worse clinical efficacy outcomes in mCRC patients receiving anti-EGFR antibody rechallenge plus trifluridine/tipiracil. A comprehensive genomic test using ctDNA immediately before anti-EGFR antibodies rechallenge might help determine its indication.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Clinical, Journal: How to Apply Supervised Machine Learning Tools to MS Imaging Files: Case Study with Cancer Spheroids Undergoing Treatment with the Monoclonal Antibody, Cetuximab. (Pubmed Central) - Apr 24, 2021
To address this problem, we developed a fully open-source approach that facilitates supervised machine learning on MS imaging files, and we demonstrated its implementation on sets of cancer spheroids that either had or had not undergone chemotherapy treatment. These supervised machine learning studies demonstrated that metabolic changes induced by the monoclonal antibody, Cetuximab, are detectable but modest at 24 hours, and by 72 hours, the drug induces a larger and more diverse metabolic response.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Preclinical, Journal: Radiotherapy enhances uptake and efficacy of Y-Cetuximab: a preclinical trial. (Pubmed Central) - Apr 24, 2021
Our results indicate that combination of radiolabeled therapeutics with clinically relevant fractionated radiotherapy has a remarkable potential to improve curative treatment outcome. Application of some radiation dose prior to injection may improve drug uptake and enable patient stratification and treatment personalization via a corresponding PET-tracer during therapy.
- |||||||||| prexasertib (LY2606368) / Eli Lilly, SOM Biotech, Ewha Womans University, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Clinical, P1 data, Clinical Trial,Phase I, Journal, Combination therapy: A phase 1b trial of prexasertib in combination with chemoradiation in patients with locally advanced head and neck squamous cell carcinoma. (Pubmed Central) - Apr 24, 2021
However, it demonstrates the proof-of-principle that prexasertib could be safely combined with cetuximab-radiotherapy. These data will provide the basis to leverage the potential radio-sensitization properties of a CHK1 inhibitor in combination with radiation or other targeted agents in a variety of therapeutic settings.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Journal: Combretastatin A4-derived payloads for antibody-drug conjugates. (Pubmed Central) - Apr 23, 2021
Cetuximab conjugates consisting of CA4 derivatives were site-specially prepared by disulfide re-bridging approach using cleavable and non-cleavable linkers...The conjugates also demonstrated significant antitumor activities in EGFR-positive xenograft models without observed toxicities. CA4 appears to be a viable payload option for ADCs research and development.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Trial completion date, Trial termination, Trial primary completion date, Metastases: IMPACT-CRC: Image Guided Treatment Optimization With Cetuximab for Patients With Metastatic Colorectal Cancer (clinicaltrials.gov) - Apr 23, 2021
P1/2, N=85, Terminated,
CA4 appears to be a viable payload option for ADCs research and development. Trial completion date: Mar 2019 --> Jan 2021 | Recruiting --> Terminated | Trial primary completion date: Mar 2019 --> Jan 2021; Primary endpoint could no longer be reached.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Trial completion date, Trial primary completion date, Metastases: Concomitant Immune Check Point Inhibitor With Radiochemotherapy in Head And Neck Cancer (clinicaltrials.gov) - Apr 22, 2021
P2, N=50, Recruiting,
Trial completion date: Dec 2021 --> Dec 2024 | Trial primary completion date: Dec 2020 --> Sep 2024 Trial completion date: Oct 2022 --> Oct 2023 | Trial primary completion date: Sep 2021 --> Sep 2022
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Trial completion date, Trial primary completion date, Surgery, Metastases: Cetuximab Before Surgery in Treating Patients With Aggressive Locally Advanced Skin Cancer (clinicaltrials.gov) - Apr 22, 2021
P=N/A, N=15, Active, not recruiting,
Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Aug 2020 --> Aug 2021 Trial completion date: Nov 2020 --> Dec 2021 | Trial primary completion date: Nov 2020 --> Dec 2021
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Clinical, Journal: Impact of EGFR and EGFR ligand expression on treatment response in patients with metastatic colorectal cancer. (Pubmed Central) - Apr 22, 2021
The expression levels of EGFRs (EGFR/ErbB1, ErbB2 and ErbB3) and their ligands (heregulin and amphiregulin) were not significantly associated with the response to cetuximab therapy. Therefore, the present study indicated that EGFR or EGFR ligand expression did not predict treatment response in patients with CRC with liver metastases following cetuximab therapy.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Opdivo (nivolumab) / Ono Pharma, BMS
Clinical, Review, Journal: Squamous cell carcinoma of the tongue with cardiac metastasis on 18F-FDG PET/CT: A case report and literature review. (Pubmed Central) - Apr 20, 2021
In this case report, 18F-FDG PET/CT proved to be useful in detecting cardiac metastasis and changed the therapeutic management of the patient. It suggests that patients with tongue malignancies in a context of poor initial prognosis should be followed-up early by 18F-FDG PET/CT with HFLC diet to facilitate detection of recurrence.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
[VIRTUAL] Euglycemic Diabetic Ketoacidosis Related to SGLT2 Inhibitor Use in Kidney Transplant Patient with Squamous Cell Carcinoma () - Apr 17, 2021 - Abstract #ISNWCN2021ISN-WCN_1263;
Her home medications included insulin glargine, dapagliflozin 10 mg, pantoprazole 40mg, prednisolone 7.5 mg daily, cyclosporine 125 mg q12 hours and atorvastatin 20mg...She was initiated on concurrent chemotherapy (Cetuximab) and radiotherapy...She required critical care admission with rigorous IV hydration, insulin infusion per DKA protocol, IV sodium bicarbonate, IV hydrocortisone and IV cyclosporine...Conclusions SGLT2 inhibitor associated eDKA is very rare in oncology patients and this is the first case reported in kidney transplant patient who was on active chemotherapy and radiotherapy for squamous cell carcinoma. We suggest to hold SGLT2i therapy during active oncology treatment especially in the setting on severe mucositis.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Clinical, P2 data, Journal: Cetuximab, docetaxel, and cisplatin versus platinum, fluorouracil, and cetuximab as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (GORTEC 2014-01 TPExtreme): a multicentre, open-label, randomised, phase 2 trial. (Pubmed Central) - Apr 16, 2021
P2
Although the trial did not meet its primary endpoint, with no significant improvement in overall survival with TPEx versus EXTREME, the TPEx regimen had a favourable safety profile. The TPEx regimen could provide an alternative to standard of care with the EXTREME regimen in the first-line treatment of patients with recurrent or metastatic HNSCC, especially for those who might not be good candidates for up-front pembrolizumab treatment.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Preclinical, Journal: Establishment of animal models of epidermal growth factor receptor inhibitor-related rashes (Pubmed Central) - Apr 16, 2021
Intraperitoneal injection of cetuximab can not induce epidermal growth factor receptor inhibitor-related skin rashes in SCID mice. Lavage of gefitinib, but not erlotinib, can be used to establish models of epidermal growth factor receptor inhibitor-related rashes in BN rats.
- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Clinical, Journal, Combination therapy: Aflibercept or bevacizumab in combination with FOLFIRI as second-line treatment of mRAS metastatic colorectal cancer patients: the ARBITRATION study protocol. (Pubmed Central) - Apr 16, 2021
P
For instance, in mRAS (mutated RAS) mCRC patients, anti-EGFR drugs (cetuximab and panitumumab) are not recommended; in this group of patients, the use of anti-angiogenic drugs (bevacizumab and aflibercept) is predominant...ARBITRATION is a prospective, observational study assessing efficacy differences between second-line fluorouracil/irinotecan (FOLFIRI)/bevacizumab versus FOLFIRI/aflibercept at progression to fluoropyrimidines, oxaliplatin and bevacizumab in mRAS mCRC patients...We present a large, prospective, observational study aiming to answer two scientific questions: (1) outcome differences between second-line treatments with FOLFIRI/bevacizumab beyond progression versus FOLFIRI/aflibercept in mRAS mCRC patients, (2) angiogenic factors' patterns that could associate with efficacy and help oncologists to apply best the therapeutic anti-angiogenic strategies. The ARBITRATION trial (version 0.0, 13 April 2020) has been registered into the clinicaltrials.gov registry on 20 May 2020 with identifier NCT04397601.
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