- |||||||||| Desferal (deferoxamine) / Kermanshah University of Medical Sciences, Novartis
Preclinical, Journal: Deferoxamine Ameliorates Compressed Spinal Cord Injury by Promoting Neovascularization in Rats. (Pubmed Central) - Jun 11, 2021
Therefore, we concluded that DFO effectively alleviated SCI by promoting neovascularization in the injured spinal cord. Considering that DFO is an FDA-approved free radical scavenger and iron chelator, it may represent a promising alternative strategy for SCI therapy in the future.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial primary completion date, IO biomarker: NeoPele: A Phase II Study of Neoadjuvant Pembrolizumab & Lenvatinib for Resectable Stage III Melanoma (clinicaltrials.gov) - Jun 9, 2021
P2, N=20, Recruiting,
Considering that DFO is an FDA-approved free radical scavenger and iron chelator, it may represent a promising alternative strategy for SCI therapy in the future. Trial primary completion date: Mar 2021 --> Nov 2021
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD)
Journal, MSi-H Biomarker, PD(L)-1 Biomarker, IO biomarker: Optimizing immunotherapy for gynecologic cancers. (Pubmed Central) - Jun 9, 2021
However, improved molecular and immunophenotypic biomarkers to more accurately identify patients who will most benefit from immunotherapeutic approaches are urgently needed. This is especially critical as we attempt to integrate immune-oncology agents, chemotherapy, targeted therapy, and radiation therapy in the management of gynecologic cancers.
- |||||||||| golvatinib (E7050) / Eisai, Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial termination, Combination therapy, Metastases: A Study of E7050 in Combination With E7080 in Participants With Advanced Solid Tumors (Dose Escalation) and in Participants With Recurrent Glioblastoma or Unresectable Stage III or Stage IV Melanoma After Prior Systemic Therapy (Expansion Cohort and Phase 2) (clinicaltrials.gov) - Jun 8, 2021
P1b/2, N=30, Terminated,
This is especially critical as we attempt to integrate immune-oncology agents, chemotherapy, targeted therapy, and radiation therapy in the management of gynecologic cancers. Completed --> Terminated; Study was terminated by the sponsor early at the end of Phase 1b due to a change in corporate strategy.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Clinical, Review, Journal, IO biomarker: Novel therapeutics for patients with well-differentiated gastroenteropancreatic neuroendocrine tumors. (Pubmed Central) - Jun 8, 2021
And though single-agent immune checkpoint inhibitors have not demonstrated significant anti-tumor activity in patients with GEP NETs, outside of certain biomarker selected subsets, somatostatin receptor-directed chimeric antigen receptor (CAR) T cells and vaccines such as SurVaxM, which targets survivin, represent two means through which NET-directed immunity may be modulated. The potential of these agents, if clinically realized, will likely improve outcomes for patients with well-differentiated GEP NETs.
- |||||||||| lenvatinib / Generic mfg.
[VIRTUAL] Lenvatinib use Associated with Multi-organ Adverse Events in Hurthle Cell Thyroid Cancer () - Jun 7, 2021 - Abstract #AACE2021AACE_445;
The management of metastatic progressive radioiodine-resistant differentiated thyroid cancer has remained a challenge for clinicians. The availability of tyrosine kinase inhibitors (TKIs) within the last decade has expanded the treatment options, but these come with significant adverse effects that may curtail their use.
- |||||||||| lenvatinib / Generic mfg.
[VIRTUAL] Delayed Lenvatinib Associated Thyrotoxicosis () - Jun 7, 2021 - Abstract #AACE2021AACE_350;
Although less common, recent case reports have evidenced an increased risk for thyrotoxicosis during early treatment with Lenvatinib. The entirety of thyrotoxic cases were associated to destructive thyroiditis presenting within the first 8 weeks of treatment and with 80% of cases occurring within the first two weeks of treatment.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen, Nexavar (sorafenib) / Bayer, Amgen
[VIRTUAL] Hepatocellular Carcinoma (HCC) () - Jun 5, 2021 - Abstract #ASCO2021ASCO_5886;
The entirety of thyrotoxic cases were associated to destructive thyroiditis presenting within the first 8 weeks of treatment and with 80% of cases occurring within the first two weeks of treatment. Clinical and biologic factors affecting the selection of first-line treatment for advanced HCC (eg, age, performance status, symptomatology, Child-Pugh score) Available data with and current clinical roles of sorafenib and lenvatinib as first-line therapy for unresectable HCC; patient selection for tyrosine kinase inhibitor (TKI) monotherapy Design of, entry criteria for and key efficacy and safety findings from the Phase III IMbrave150 trial of first-line atezolizumab/ bevacizumab versus sorafenib for advanced unresectable HCC; FDA approval of atezolizumab/ bevacizumab and patient selection for first-line therapy with atezolizumab/bevacizumab Mechanism or action of sintilimab; recently presented results from the Phase II/III ORIENT-32 trial evaluating the efficacy and safety of sintilimab in combination with bevacizumab biosimilar versus sorafenib as first-line treatment for advanced HCC Optimal management of patients with HCC and compromised hepatic function, poor performance status and/or other comorbidities in the first-line setting Selection and sequencing of approved agents and regimens for patients with disease progression on first-line therapy; impact of increased utilization of first-line atezolizumab/bevacizumab on second- and later-line therapy decision making Long-term outcomes with approved multikinase inhibitors (eg, regorafenib, cabozantinib) in previously treated advanced HCC Published efficacy and safety data with the use of an anti-PD-1/PD-L1 antibody alone or in combination with an anti-CTLA4 antibody for patients with relapsed or refractory HCC Clinical implications of the negative overall survival results from the Phase III CheckMate 459 trial of nivolumab versus sorafenib as first-line therapy for patients with advanced HCC; FDA advisory committee review of the single-agent nivolumab indication for patients with HCC who have previously received sorafenib FDA approved indication for the combination of nivolumab and ipilimumab for patients with previously treated HCC based on the results of the Phase I/II CheckMate 040 trial (Cohort 4); current clinical role of this combination Design, entry criteria and key endpoints of the Phase III CheckMate 9DW trial comparing nivolumab in combination with ipilimumab to sorafenib or lenvatinib as first-line therapy for advanced HCC Active Phase III trials investigating the benefit of combining an immune checkpoint inhibitor with a TKI as first-line therapy for patients with newly diagnosed advanced HCC (eg, LEAP-002, COSMIC-312); potential clinical role of these regimens Early efficacy and safety findings with the combination of durvalumab and tremelimumab as first- or second-line therapy for patients with advanced HCC Design, eligibility criteria and key efficacy and safety endpoints of the Phase III HIMALAYA trial evaluating durvalumab alone or in combination with tremelimumab versus sorafenib as first-line therapy for patients with advanced HCC Biologic rationale for, available clinical trial data with and ongoing investigations of an immune checkpoint inhibitor in combination with a TKI (eg, lenvatinib, cabozantinib) for newly diagnosed and previously treated advanced HCC Optimal selection of third-line therapy for patients with HCC; available data sets with FDA-approved agents and regimens in patients with multiply-relapsed disease Prognosis of patients with AFP-high (≥400 ng/mL) HCC; impact of AFP level on therapy decision-making and treatment outcomes Published results from the Phase III REACH-2 trial of ramucirumab versus placebo for patients with AFP-elevated (≥400) relapsed or refractory HCC; patient selection for treatment with ramucirumab Other promising agents and strategies currently under investigation for patients with HCC
- |||||||||| paclitaxel / Generic mfg.
[VIRTUAL] Endometrial Cancer (EC) () - Jun 5, 2021 - Abstract #ASCO2021ASCO_5876;
Clinical and biologic factors affecting the selection of first-line treatment for advanced HCC (eg, age, performance status, symptomatology, Child-Pugh score) Available data with and current clinical roles of sorafenib and lenvatinib as first-line therapy for unresectable HCC; patient selection for tyrosine kinase inhibitor (TKI) monotherapy Design of, entry criteria for and key efficacy and safety findings from the Phase III IMbrave150 trial of first-line atezolizumab/ bevacizumab versus sorafenib for advanced unresectable HCC; FDA approval of atezolizumab/ bevacizumab and patient selection for first-line therapy with atezolizumab/bevacizumab Mechanism or action of sintilimab; recently presented results from the Phase II/III ORIENT-32 trial evaluating the efficacy and safety of sintilimab in combination with bevacizumab biosimilar versus sorafenib as first-line treatment for advanced HCC Optimal management of patients with HCC and compromised hepatic function, poor performance status and/or other comorbidities in the first-line setting Selection and sequencing of approved agents and regimens for patients with disease progression on first-line therapy; impact of increased utilization of first-line atezolizumab/bevacizumab on second- and later-line therapy decision making Long-term outcomes with approved multikinase inhibitors (eg, regorafenib, cabozantinib) in previously treated advanced HCC Published efficacy and safety data with the use of an anti-PD-1/PD-L1 antibody alone or in combination with an anti-CTLA4 antibody for patients with relapsed or refractory HCC Clinical implications of the negative overall survival results from the Phase III CheckMate 459 trial of nivolumab versus sorafenib as first-line therapy for patients with advanced HCC; FDA advisory committee review of the single-agent nivolumab indication for patients with HCC who have previously received sorafenib FDA approved indication for the combination of nivolumab and ipilimumab for patients with previously treated HCC based on the results of the Phase I/II CheckMate 040 trial (Cohort 4); current clinical role of this combination Design, entry criteria and key endpoints of the Phase III CheckMate 9DW trial comparing nivolumab in combination with ipilimumab to sorafenib or lenvatinib as first-line therapy for advanced HCC Active Phase III trials investigating the benefit of combining an immune checkpoint inhibitor with a TKI as first-line therapy for patients with newly diagnosed advanced HCC (eg, LEAP-002, COSMIC-312); potential clinical role of these regimens Early efficacy and safety findings with the combination of durvalumab and tremelimumab as first- or second-line therapy for patients with advanced HCC Design, eligibility criteria and key efficacy and safety endpoints of the Phase III HIMALAYA trial evaluating durvalumab alone or in combination with tremelimumab versus sorafenib as first-line therapy for patients with advanced HCC Biologic rationale for, available clinical trial data with and ongoing investigations of an immune checkpoint inhibitor in combination with a TKI (eg, lenvatinib, cabozantinib) for newly diagnosed and previously treated advanced HCC Optimal selection of third-line therapy for patients with HCC; available data sets with FDA-approved agents and regimens in patients with multiply-relapsed disease Prognosis of patients with AFP-high (≥400 ng/mL) HCC; impact of AFP level on therapy decision-making and treatment outcomes Published results from the Phase III REACH-2 trial of ramucirumab versus placebo for patients with AFP-elevated (≥400) relapsed or refractory HCC; patient selection for treatment with ramucirumab Other promising agents and strategies currently under investigation for patients with HCC Incidence of high microsatellite instability (MSI) or mismatch repair (MMR) deficiency in patients with advanced EC; current indications for MSI/MMR testing Efficacy and safety outcomes with pembrolizumab monotherapy for patients with MSI-high (MSI-H)/MMR-deficient (dMMR) advanced EC Mechanism of action of dostarlimab; design of the Phase I/II GARNET trial evaluating dostarlimab for patients with advanced EC Available safety and efficacy data from GARNET: Response rates, duration of response and recent FDA approval of dostarlimab for patients with MSI-H/dMMR tumors Response rates with dostarlimab for patients with microsatellite-stable tumors in the GARNET study; potential clinical role of dostarlimab Key efficacy and safety findings from the Phase II KEYNOTE-146 study assessing pembrolizumab with lenvatinib for relapsed/refractory (R/R) EC; differences in response rates between patients with and without MSI-H/dMMR disease FDA approval of pembrolizumab/lenvatinib for patients with advanced EC that is not MSI-H/dMMR who experience disease progression after prior systemic therapy but are not candidates for curative surgery or radiation therapy; optimal integration of this regimen into clinical practice Incidence and severity of toxicities associated with pembrolizumab/lenvatinib; reported rates of fatigue, hypertension, gastrointestinal toxicity, hand-foot syndrome, hemorrhage, et cetera; dose reduction, discontinuation and other management strategies Similarities and differences in the design, eligibility requirements and primary and secondary endpoints of the Phase III KEYNOTE-775 and LEAP-001 trials comparing pembrolizumab/lenvatinib to standard chemotherapy for newly diagnosed or recurrent advanced EC Current understanding of the effect of combining chemotherapy with immune checkpoint inhibitors Design, eligibility criteria and key efficacy and safety endpoints in ongoing Phase III trials evaluating carboplatin/paclitaxel with or without dostarlimab or pembrolizumab for patients with recurrent or primary advanced EC
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), tisotumab vedotin (HuMax-TF-ADC) / Genmab, Seagen
[VIRTUAL] A Conversation with the Investigators: Endometrial and Cervical Cancers () - Jun 5, 2021 - Abstract #ASCO2021ASCO_5844;
Design and implement a plan of care to recognize and manage side effects and toxicities associated with immune checkpoint inhibitors in the management of endometrial and cervical cancer in order to support quality of life and continuation of therapy. Recall the design of ongoing clinical trials evaluating novel agents and strategies for patients with gynecologic cancers, and counsel appropriate individuals about availability and participation.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
[VIRTUAL] Immune Checkpoint Inhibition in Advanced Bladder and Kidney Cancer: Responses and Further Management () - Jun 5, 2021 - Abstract #ASCO2021ASCO_5761;
Combinations of immune checkpoint inhibitors or immune checkpoint inhibitors with VEGF-targeting agents have become first-line therapy for mRCC and they result in substantial and durable responses. Currently, single-agent immune checkpoint inhibitors have established efficacy in the treatment of mUC, with durable responses observed.
- |||||||||| lenvatinib / Generic mfg.
Journal: SYMPTOMATIC BILIARY DISORDERS DURING LENVATINIB TREATMENT FOR THYROID CANCER: AN UNDERESTIMATED PROBLEM? (Pubmed Central) - Jun 5, 2021
In our cohort, an unexpectedly high proportion of RAI refractory DTC patients treated with lenvatinib developed a symptomatic biliary disorder with the need of surgical intervention. Further studies are required to optimize the diagnosis and treatment of patients at higher risk of developing a symptomatic GB/BD disease during assumption of lenvatinib.
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