- |||||||||| Plasma Exchange for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitor Therapy: Implications for Clinical Care and Clinical Trial Design (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_2032;
ICI constructs were IgG1 anti-PD-L1 (envafolimab, durvalumab) and IgG4 anti-PD-1 (nivolumab, cemiplimab)...Grade 4 bleeding occurred in the patient receiving enoxaparin and DAPT and led to discontinuation of TPE after 2 sessions. Our experience supports the following when considering TPE for irAEs: 1) exclusion of patients with high bleeding risk, or use of 100% FFP replacement and every other day TPE; 2) meticulous non-biomarker irAE assessment during and after TPE; 3) RCT design includes irAE relapse timing and rates and long term follow-up to assess cumulative immunosuppression and tumor outcome; 4) serial drug levels and correlative studies (e.g. cytokines, autoantibodies) to better understand TPE mechanisms, persistence of irAEs, and long term ICI anti-tumor benefit.
- |||||||||| Libtayo (cemiplimab-rwlc) / Regeneron
Trial termination, IO biomarker: EMPOWER-lung 4: A Study of REGN2810 and Ipilimumab in Patients With Lung Cancer (clinicaltrials.gov) - Nov 3, 2022 P2, N=28, Terminated, Our experience supports the following when considering TPE for irAEs: 1) exclusion of patients with high bleeding risk, or use of 100% FFP replacement and every other day TPE; 2) meticulous non-biomarker irAE assessment during and after TPE; 3) RCT design includes irAE relapse timing and rates and long term follow-up to assess cumulative immunosuppression and tumor outcome; 4) serial drug levels and correlative studies (e.g. cytokines, autoantibodies) to better understand TPE mechanisms, persistence of irAEs, and long term ICI anti-tumor benefit. Completed --> Terminated; Business decision
- |||||||||| Libtayo (cemiplimab) / Regeneron
Journal: Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma. (Pubmed Central) - Nov 1, 2022 P2 Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).
- |||||||||| Libtayo (cemiplimab) / Regeneron, Keytruda (pembrolizumab) / Merck (MSD), Opdivo (nivolumab) / Ono Pharma, BMS
Review, Journal: Anti-PD1 Agents in the Treatment of Cutaneous Squamous Cell Carcinoma. (Pubmed Central) - Nov 1, 2022 This review described other anti-PD1 agents, such as pembrolizumab and nivolumab, that have depicted promising effects in advanced SCC, resulting in reduction of tumor size with minimal adverse effects...(SKINmed. 2022;20:338-342).
- |||||||||| Libtayo (cemiplimab) / Regeneron, Keytruda (pembrolizumab) / Merck (MSD), Opdivo (nivolumab) / Ono Pharma, BMS
Review, Journal: Anti-PD1 Agents in the Treatment of Cutaneous Squamous Cell Carcinoma. (Pubmed Central) - Nov 1, 2022 This review described other anti-PD1 agents, such as pembrolizumab and nivolumab, that have depicted promising effects in advanced SCC, resulting in reduction of tumor size with minimal adverse effects. Immunotherapy targeting the PD-1-PD-L1 axis must be considered for advanced cutaneous SCC patients that are refractory to first-line of procedural treatment options.
- |||||||||| Biomarker, Review, Journal, PD(L)-1 Biomarker, IO biomarker: Recurrent or primary metastatic cervical cancer: current and future treatments. (Pubmed Central) - Oct 25, 2022
Tisotumab vedotin, an antibody-drug conjugate targeting the tissue factor, is another emerging drug...The Cancer Genome Atlas Research Network identified several genes significantly mutated, potentially targetable. These molecular data have highlighted the molecular heterogeneity of CC.
- |||||||||| Libtayo (cemiplimab) / Regeneron
Liver metastases (mets) and treatment effect of cemiplimab-based therapy: an analysis from three Phase 3 trials (EMPOWER-Lung 1, EMPOWER-Lung 3 Part 2, and EMPOWER-Cervical 1) (Foyer ABC) - Oct 21, 2022 - Abstract #ESMOIO2022ESMO_IO_321; P3 Table: 168P OS, PFS, and ORR in patients with baseline liver mets EMPOWER-Lung1† n=563 EMPOWER-Lung3 Part 2 n=466 EMPOWER-Cervical1 n=608 Liver mets n=95Cemi n=48 vschemo n=47 Liver mets n=70Cemi+chemo n=47 vsPbo+chemo n=23 Liver mets n=143Cemi n=78 vschemo n=65 OS median, months NR vs 7.4 14.4 vs 8.9 5.2 vs 6.5 OS HR, (95% CI) 0.38 (0.19–0.75) 0.61 (0.31–1.20) 0.92 (0.62–1.36) PFS median, months 6.2 vs 4.2 5.4 vs 4.2 1.4 vs 1.9 PFS HR, (95% CI) 0.51 (0.30–0.88) 0.64 (0.34–1.17) 0.89 (0.62–1.28) ORR, % 29 vs 15 34 vs 13 9 vs 3 †PD-L1≥50% population CI, confidence interval; Pbo, placebo. Conclusions Despite a lower efficacy of Cemiplimab in patients with liver mets from primary lung/cervix cancer than those without, the relative benefit over prior standard-of-care regimens was preserved, and for some patients, even enhanced.
- |||||||||| Libtayo (cemiplimab) / Regeneron, fianlimab (REGN3767) / Regeneron, Sanofi
Phase 1 study of fianlimab, a human lymphocyte activation gene-3 (LAG-3) monoclonal antibody, in combination with cemiplimab in advanced melanoma (mel): subgroup analysis (Foyer ABC) - Oct 21, 2022 - Abstract #ESMOIO2022ESMO_IO_303; P1 In pts with LDH>ULN at BL and any M1c, the ORR for EC6+15 was 53.8%, the DCR was 69.2%, and the mDOR was NR (95% CI, 5.7–NE). Conclusions Despite small numbers in subgroups, the efficacy analysis from EC6 and EC15 combined demonstrates high activity of fianlimab in combination with cemiplimab in pts with advanced mel and poor prognosis features at BL.
- |||||||||| Review, Journal: Chemotherapy and immune check point inhibitors in the management of cervical cancer. (Pubmed Central) - Oct 21, 2022
Management of locally advanced cervix cancer underwent major change 2 decades back when concurrent chemotherapy (CCRT) (with cisplatin alone or in combination) along with definite radiation therapy (external + brachytherapy) was found to be superior compared to radiation alone in a series of randomized trials...To improve the outcome further - recent approaches have explored use of weekly paclitaxel and carboplatin for 4 to 6 weeks as dose dense chemotherapy prior to CCRT, adjuvant chemotherapy after CCRT in high risk patients...More recently, addition of treatment with immune check inhibitors (to boost the ability of T cells to destroy cancer cells) have improved responses and survival in the treatment of recurrent and metastatic cervical cancer. Whether these and other similar novel agents targeting molecular pathways could be brought in front line treatment along with cytotoxic chemotherapy along with bevacizumab are potential areas of current research.
- |||||||||| Incidence and management of severe immune-related adverse events in a regional Australian setting. (Great Hall 3&4) - Oct 20, 2022 - Abstract #COSA2022COSA_271;
A retrospective cohort of regional Victorian patients (Latrobe Regional Hospital, Bairnsdale Regional Health Service, Central Gippsland Health) receiving at least one dose of ICI (pembrolizumab, nivolumab, ipilimumab, atezolizumab, cemiplimab, durvalumab, avelumab) between 1 July 2018 - 30 June 2021...32/373 (9%) required IV methylprednisolone and infliximab in 3... Optimal management of ICI related severe irAE in a regional setting is achievable with contemporary protocols and responsive metropolitan support.
- |||||||||| Libtayo (cemiplimab-rwlc) / Regeneron
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date: TOSCA: Comparative Efficacy of Cemiplimab to Historical Standard of Care in France (clinicaltrials.gov) - Oct 20, 2022 P=N/A, N=305, Active, not recruiting, Initiation date: Sep 2022 --> Jan 2023 Completed --> Active, not recruiting | N=498 --> 305 | Trial completion date: Sep 2022 --> Mar 2023 | Trial primary completion date: Sep 2022 --> Mar 2023
- |||||||||| Libtayo (cemiplimab) / Regeneron, Keytruda (pembrolizumab) / Merck (MSD), fianlimab (REGN3767) / Regeneron, Sanofi
Open. Pembro vs fianlimab/cemiplimab (Twitter) - Oct 19, 2022
- |||||||||| Libtayo (cemiplimab) / Regeneron
CEMIPLIMAB IN CUTANEOUS SQUAMOUS CELL CARCINOMA (CSCC) () - Oct 19, 2022 - Abstract #AIOM2022AIOM_93; No grade 3-4 toxicities were observed. Cemiplimab is effective and well tolerated, and may pro- log survival with a relatively good quality of life in patients with SCC of the skin.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD)
Journal, Monotherapy, PD(L)-1 Biomarker, IO biomarker: Pembrolizumab as monotherapy in locally advanced cutaneous squamous cell carcinoma. (Pubmed Central) - Oct 19, 2022 In addition, these trials excluded immunosuppressed patients due to hematological malignancies or prior organ transplant, which are populations with significantly increased risk of cSCC. Finally, a variety of novel approaches using checkpoint inhibition in cSCC are being investigated, with some encouraging preliminary results.
- |||||||||| Libtayo (cemiplimab) / Regeneron
Journal: Posterior Uveitis Associated with Cemiplimab. (Pubmed Central) - Oct 18, 2022 Similar to other ICPIs, uveitis may be associated with cemiplimab. In the setting of posterior uveitis, treatment may require cessation of cemiplimab and intensive steroid treatment.
- |||||||||| Libtayo (cemiplimab) / Regeneron
High PD-L2 protein expression in cancer cells is an independent marker of unfavorable prognosis in luminal breast tumors (Hall 1) - Oct 10, 2022 - Abstract #SABCS2022SABCS_585; P2 The observed frequent expression of PD-L2 protein in BC provided scientific rationale for the design of our ongoing phase II clinical trial (NCT04243616) of neoadjuvant combined PD-1 inhibitor (cemiplimab; Regeneron Pharmaceuticals Inc) and chemotherapy in patients diagnosed with PD-L1+ and/or PD-L2+ BC...Preliminary analyses of ER+ tumors from our ongoing clinical trial showed frequent discordance between baseline PD-L1 and PD-L2 protein expression in both cancer cells and immune cells. Collectively, our analyses indicate that PD-L2 has prognostic value for ER+ BC, and our progress justify further studies to determine whether PD-L2, alone or in combination with PD-L1, may serve as a predictive marker of response to PD-1 inhibitors.
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