- |||||||||| Avastin (bevacizumab) / Roche, Erbitux (cetuximab) / Eli Lilly, EMD Serono
Clinical, HEOR, Patient reported outcomes, Metastases: Marques, R.P., Heudtlass, P., et al. Patient-reported outcomes and health-related quality of life for cetuximab versus bevacizumab in metastatic colorectal cancer: a prospective cohort study. J Cancer Res Clin Oncol 145, 1719–1728 (2019). https://t.co/PxrbpjYWBQ (Twitter) - Mar 21, 2023
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Journal: Cetuximab-induced bullous pemphigoid. (Pubmed Central) - Mar 21, 2023
However, in the extended wildtype group we did observe clinically relevant higher survival compared to the initial trial report, indicating that it is important to analyze a broader panel of RAS and BRAF variants using more recent sequencing techniques when assessing survival benefit after anti-EGFR therapy. No abstract available
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Review, Journal: TRESBIEN (OGSG 2101): encorafenib, binimetinib and cetuximab for early recurrent stage II/III BRAF V600E-mutated colorectal cancer. (Pubmed Central) - Mar 16, 2023
Here we describe our plan for the TRESBIEN study (OGSG 2101), which is an open-label, multicenter, single-arm, phase II study designed to evaluate whether encorafenib, binimetinib and cetuximab are effective for patients with early recurrent BRAF V600E-mutated colorectal cancer, during or after adjuvant chemotherapy. The planned number of subjects is 25.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Retrospective data, Journal: Radiotherapy Plus Cetuximab for Squamous Cell Carcinoma of the Oral Cavity: A Multicenter Retrospective Study of 79 Patients in Japan. (Pubmed Central) - Mar 16, 2023
The most common reason for noncompletion was an inadequate radiation dose due to worsening general conditions in R/M patients. Although the standard treatment for LA or R/M oral cancer is concomitant RT with high-dose cisplatin (CCRT) and the efficacy of RT and CET therapy for oral cancer is not considered to be as high as that for other head and neck cancers, it was thought that RT and CET therapy could be possible treatments for patients who cannot use high-dose cisplatin.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Trial completion date, Trial primary completion date, Checkpoint inhibition, Metastases: Paclitaxel Plus Cetuximab After First-line Checkpoint Inhibitor Failure (clinicaltrials.gov) - Mar 16, 2023
P2, N=50, Recruiting,
Although the standard treatment for LA or R/M oral cancer is concomitant RT with high-dose cisplatin (CCRT) and the efficacy of RT and CET therapy for oral cancer is not considered to be as high as that for other head and neck cancers, it was thought that RT and CET therapy could be possible treatments for patients who cannot use high-dose cisplatin. Trial completion date: Dec 2023 --> Jul 2024 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| Teysuno (gimeracil/oteracil/tegafur) / Nordic Group, Otsuka, Tomudex (raltitrexed) / Pfizer, AstraZeneca, Elunate (fruquintinib) / Takeda
Clinical, Journal, Metastases: Using a combination of fruquintinib, raltitrexed, and S-1 as a third-line treatment for metastatic colorectal cancer with co-existence of Hodgkin lymphoma: a case report. (Pubmed Central) - Mar 15, 2023
Fruquintinib, regorafenib, trifluridine/tipiracil (TAS-102), panitumumab and cetuximab combined with single-agent chemotherapy regimens are currently recommended as third-line therapies for patients exhibiting disease progression...The mFOLFOX6 regimen was administered...Liver metastases (intestinal-type adenocarcinoma) were detected in November 2018, and second-line therapy with the FOLFIRI regimen was initiated in January 2019...Third-line therapy with fruquintinib, raltitrexed, and S-1 achieved a PR that permitted surgical resection and enabled a relatively long progression-free survival. The findings suggest that the three agents regimen might be clinically effective as late-line therapy for mCRC.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Journal, IO biomarker: A Nanotherapeutic Strategy to Reverse NK Cell Exhaustion. (Pubmed Central) - Mar 15, 2023
Here, we developed a self-assembled selenium containing nanoparticles (NPs) composed of Cetuximab, C5SeSeC5 and inhibitor LY345899 to reverse NK cell exhaustion...As a result, the enhanced NK cell-mediated immunotherapy in conjunction with the Cetuximab-mediated ADCC effect can not only effectively inhibit the growth of xenograft tumors, but also significantly suppress the growth of untreated distant tumors via the abscopal effect. This work, the combination of seleninic acid, LY345899 and Cetuximab, provides a new strategy for reversing NK cell exhaustion and has great potential for use in the treatment of metastatic tumors.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, temuterkib (LY3214996) / Eli Lilly, Verzenio (abemaciclib) / Eli Lilly
Trial completion date, Trial primary completion date, Combination therapy, Metastases: LY3214996 and Cetuximab Alone or in Combination With Abemaciclib for the Treatment of Unresectable or Metastatic Colorectal Cancer (clinicaltrials.gov) - Mar 15, 2023
P1b/2, N=46, Recruiting,
This work, the combination of seleninic acid, LY345899 and Cetuximab, provides a new strategy for reversing NK cell exhaustion and has great potential for use in the treatment of metastatic tumors. Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Herceptin (trastuzumab) / Roche
Generation of a mutant SIRPa fusion protein with highly-improved affinity and favorable safety profile (Section 23; Poster Board #1) - Mar 14, 2023 - Abstract #AACR2023AACR_8463;
It elicits improved and dose-dependent efficacy in phagocytosis or tumor suppression combining with therapeutic antibodies, such as trastuzumab or cetuximab. Favorable safety profile with no phagocytosis of RBC or platelets in vitro as well as no hematological toxicity observation in cynomolgus monkeys allows broader dose range exploration in early clinical phase.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Mechanism of anti-EGFR antibody endostatin fusion protein action on inhibition of vasculogenic mimicry and tumor cell motility in triple negative breast cancer (Section 21; Poster Board #26) - Mar 14, 2023 - Abstract #AACR2023AACR_8320;
Although expression of and signaling by the epidermal growth factor receptor (EGFR) is commonly seen in TNBC, anti-EGFR antibodies such as Cetuximab have had limited therapeutic efficacy, used alone or in combination with chemotherapy.Primary TNBC tumor growth and metastases require supporting vasculature, which develops through a combination of endothelial angiogenesis and vasculogenic mimicry (VM)...These results indicate that ?EGFR-E-P125A suppressed both EGFR and ?5?1 integrin signaling. Simultaneous inhibition of EGFR and ?5?1integrin signaling by ?EGFR-E-P125A fusion is a promising approach to inhibition of TNBC growth and metastases.
- |||||||||| izalontamab (SI-B001) / Biokin Pharma
Anti-tumor efficacy of SI-B001, a novel EGFR (Section 21; Poster Board #16) - Mar 14, 2023 - Abstract #AACR2023AACR_8310;
Currently, 6 phase II clinical trials of SI-B001, either alone or in combination with chemotherapy, have been conducted in different epithelial carcinomas. These studies have shown a potential break-through activity in NSCLC and HNSCC with a very good safety profile.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Tumor-immune microenvironmental profiling during chemo- and targeted therapy for head and neck squamous cell carcinoma (Section 24; Poster Board #12) - Mar 14, 2023 - Abstract #AACR2023AACR_7393;
In conclusion, longitudinal tissue-based monitoring revealed the presence of differential tumor-immune complexity profiles related to therapeutic efficacy and resistance. Hypo-inflamed profiles might require upfront chemo/targeted therapy before immunotherapy, and myeloid-inflamed profiles might require myeloid cell-targeted therapies, mandating the establishment of rapid clinical assessment of tumor-immune microenvironment.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Gilotrif (afatinib) / Boehringer Ingelheim
Mechanisms of EGFR inhibitor sensitivity and resistance in chordoma (Section 13; Poster Board #8) - Mar 14, 2023 - Abstract #AACR2023AACR_7212;
Collectively, our data identify a striking degree of differential sensitivity to EGFRi in chordoma, and begin to shed light on factors associated with primary and acquired resistance. These results provide a framework for guiding patient selection and identifying potential combination therapy regimens to improve EGFRi efficacy and address resistance.
- |||||||||| D3S-002 / D3 Bio
Vertical inhibition of the MAPK pathway with D3S-002, a potent and selective ERK1/2 inhibitor, to improve anti-tumor activity of and overcome resistance to KRAS G12C inhibitors (Section 38; Poster Board #19) - Mar 14, 2023 - Abstract #AACR2023AACR_7083;
Adding D3S-002 to D3S-001 or MRTX849 resulted in over 80% tumor growth inhibition and significantly prolonged survival, suggesting the combination treatment can be beneficial for KRAS G12C inhibitor pre-treated patient population.Collectively, vertical inhibition by concurrently targeting KRAS G12C and ERK1/2 with respective inhibitor D3S-001 and D3S-002 demonstrated enhanced anti-tumor activity in NSCLC and CRC models with different sensitivity to KRAS G12C inhibitor monotherapy. These results provide a strong rationale for further investigation of the combination strategy of D3S-001 and D3S-002 in KRAS G12C-mutant solid tumors in the clinic.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Improved colorectal cancer survival prediction with deep learning-based WSI analysis on PETACC8 and PRODIGE13 cohorts (Section 33; Poster Board #13) - Mar 14, 2023 - Abstract #AACR2023AACR_6840;
Patients from both cohorts received standard chemotherapy treatment, with half of the PETACC8 population also receiving CETUXIMAB antibody treatment...We observed a significant c-index gain when combining our prediction and the pT classification in a linear Cox model as compared to pT alone, with c-index increasing from 0.61 to 0.66 (p=0.03).Overall, we demonstrated that our model is able to robustly predict OS from WSI in stage III colon cancers and provides increased prognostic power, on top of more traditional clinical markers such as tumor grading. Further investigation of the WSI regions targeted by our model could provide valuable insights into postoperative histopathological features of prognostic significance.
- |||||||||| Role of individual HER family members and pan-HER targeting treatment strategy in NRG1 fusion positive cancer (Section 21; Poster Board #16) - Mar 14, 2023 - Abstract #AACR2023AACR_6231;
Treatment with cetuximab, an antibody that targets EGFR, in combination with trastuzumab and pertuzumab yielded a synergistic effect on tumor cell killing. These data indicate that HER4 and EGFR can play a role in NRG1 fusion-driven signaling through crosstalk with HER2/HER3 and thus, pan-HER/EGFR inhibitors are more effective than EGFR/HER2 or HER2/HER4-selective inhibitors, highlighting the therapeutic potential of targeting multiple members of the HER family in NRG1 fusion driven cancers.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Gilotrif (afatinib) / Boehringer Ingelheim, Stivarga (regorafenib) / Bayer
The role of HER3 mutations in the progression of colon cancer and modulation of drug sensitivity and resistance (Section 19; Poster Board #11) - Mar 14, 2023 - Abstract #AACR2023AACR_6062;
It has been noted that mutant HER2 and HER3 could confer sensitivity to HER familyinhibitors, i.e. afatinib, in bladder cancer, and we have seen a difference in IC50 values of afatinibbetween cell lines containing wild-type or mutant HER3. If mutant HER3 is involved in therapeuticresistance or sensitivity and tumor progression, our findings may present a new biomarker for targetedtreatments in colorectal cancer with the eventual goal of increased overall patient survival.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Fluorescence lifetime imaging microscopy to assess drug response in patient-derived colorectal cancer organoids (Section 2; Poster Board #5) - Mar 14, 2023 - Abstract #AACR2023AACR_5338;
PDTOs were treated with clinically-relevant drugs, SN-38 (an active metabolite of irinotecan), 5-FU, and cetuximab (CTX)...Taken together, FLIM supported label-free imaging of multicellular 3D organoid models for the purposes of determining dynamic tumor drug response. We are adapting this workflow to a high-throughput multimodal imaging platform for drug screening to make more informed decisions on patient care.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Overcoming cetuximab resistance in colorectal cancer through inhibition of HGF processing (Section 9; Poster Board #12) - Mar 14, 2023 - Abstract #AACR2023AACR_5256;
We are currently testing if upstream inhibition with recombinant human HAI-1 addition can suppress HGF cleavage and overcome cetuximab resistance induced by HGF overexpression. Collectively, our findings suggest that inhibiting HGF cleavage and processing may be a unique strategy for overcoming EGFR-targeted therapy resistance in colorectal cancer.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, tiragolumab (RG6058) / Roche, Tecentriq (atezolizumab) / Roche
TIGIT knockout enhances anti-tumor response of Natural Killer cells and prevents fratricide when combined with therapeutic ADCC-competent TIGIT antibodies (Section 22; Poster Board #13) - Mar 14, 2023 - Abstract #AACR2023AACR_5075;
Although preclinical studies using combinations of anti-TIGIT and anti-PD-(L)1 showed promising results, the phase III SKYSCRAPER-01 trial using the combination of tiragolumab and atezolizumab for NSCLC did not meet its co-primary endpoint of progression free survival (PFS) while the overall survival (OS) at the time of this publication was immature with the study still ongoing...Compared to WT NK cells, TIGIT knockout NK cells had improved in vitro killing of 3D lung cancer spheroids and increased ADCC when combined with cetuximab...Moreover, fratricide of WT NK cells was observed in the presence of ADCC-competent anti-TIGIT and could be ameliorated by TIGIT knockout. Altogether, this study demonstrated that the highly cytotoxic fratricide resistant TIGIT knockout NK cells have translation potential alone or in combination with ADCC-competent anti-TIGIT antibodies to enhance the efficacy of anti-TIGIT therapeutics.
- |||||||||| Synergism between inhibitors of the EGFR-RAS-RAF-MEK pathway and the WNT pathway (Section 46; Poster Board #5) - Mar 14, 2023 - Abstract #AACR2023AACR_4815;
P1b
Secondary endpoints included PK, overall response rate, CR and PR rate, and duration of response by RECIST 1.1 and irRECIST 1.1. The clinical protocol and available data of CGX1321 in combination with encorafenib and cetuximab in CRC patients with RSPO fusions and BRAFV600E mutations will be discussed.
- |||||||||| IAE0972 / SunHo BioPharma
IAE0972, A novel EGFR/IL10 immunocytokine of monovalent anti-EGFR antibody fused with IL10 homodimer (Section 25; Poster Board #27) - Mar 14, 2023 - Abstract #AACR2023AACR_4034;
P1/2
The indications of IAE0972 include colorectal cancer, head and neck squamous cell carcinoma, squamous non-small cell lung cancer, and other EGFR positive tumors. A Phase I/IIa clinical trial to evaluate the safety, tolerability and preliminary efficacy of IAE0972 in patients with locally advanced or metastatic malignant tumors is on-going (NCT05396339).
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Characterizing antibody internalization for rational selection of ADC linker design (Section 14; Poster Board #9) - Mar 14, 2023 - Abstract #AACR2023AACR_3761;
A Phase I/IIa clinical trial to evaluate the safety, tolerability and preliminary efficacy of IAE0972 in patients with locally advanced or metastatic malignant tumors is on-going (NCT05396339). Here, we determined the cellular internalization of two antibodies, anti-perlecan antibody (
- |||||||||| SCR-8388 / Simcere
SCR-8388, a potent and selective SOS1::KRAS inhibitor, is effective in KRAS-addicted cancers (Section 20; Poster Board #21) - Mar 14, 2023 - Abstract #AACR2023AACR_3718;
Notably, SCR-8388 demonstrated synergistic effects with the anti-EGFR antibody (cetuximab) both in Kras-mutant and WT cell lines in vitro and in vivo. In summary, SCR-8388 is a highly potent and selective SOS1 inhibitor, and effectively inhibits Kras-mutant tumors as mono- or combo therapeutics.
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