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First-in-human phase I study of TNO155 (SHP2 allosteric inhibitor; 1.5-70 mg qd or 30-50 mg bid) in 118 patients with advanced solid tumors. The most frequent treatment-related adverse events (TRAEs) were increased creatine phosphokinase (33 patients [28%]), peripheral edema, diarrhea (31 each [26%]) and acneiform dermatitis (27 [23%]). Grade ≥3 TRAEs included decreased platelets (5 [4%]), increased AST, diarrhea and decreased neutrophil count (4 each [3%]). Congress Alert

First-in-human phase I study of ALT-801 (GLP-1/glucagon receptor agonist; 1.2 or 1.8 mg SC qwk) in overweight and obese subjects. Transient nausea events were reported in 14.3% subjects receiving ALT-801 at 1.2 mg and 22.2% subjects in the 1.8 mg group. [Data from an Altimmune communication announcing positive interim results from a phase I study of ALT-801] Company Communication

Preliminary results from a first-in-human phase I/II study of BDC-1001 (trastuzumab biosimilar conjugated to a TLR7/8 agonist; 0.15-5 mg/kg IV), alone or combined with pembrolizumab (PD-1 inhibitor), in 20 patients with advanced solid tumors. BDC-1001-related infusion reactions were reported. Congress Alert

First case report of a man who developed colitis with colonic pseudolipomatosis induced by atezolizumab (PD-L1 inhibitor).

The special warnings and precautions for use section of the EMA EPAR for Efmody indicates that it may cause acute adrenal insufficiency and adrenal crisis (which may be fatal after sudden treatment discontinuation); and impaired cortisol exposure in patients with increased gastrointestinal motility. Undesirable effects reported with corticosteroids are impaired glucose tolerance, diabetes, increased calcium excretion, reduced bone remodeling rate, reduced bone mineral density, severe psychiatric adverse reactions (including euphoria, mania, psychosis, hallucinations, and delirium), anaphylactoid reactions, growth retardation, weight gain, decreased height velocity, Cushing syndrome, and visual disturbances including blurred vision, cataract, glaucoma and central serous chorioretinopathy. [Data from EMA European public assessment report for Efmody (hydrocortisone; glucocorticoid receptor modulator)] Regulatory Agency Communication

First-in-human phase I trial of vorasidenib (isocitrate dehydrogenase 1/2 inhibitor; 25-400 mg PO qd) in 93 patients with mutant IDH1/2 advanced solid tumors, including 52 patients with glioma. The most common treatment-emergent adverse events (TEAEs) were headache (24/52 patients [46.2%] with glioma; 6/41 [14.6%] without glioma), ALT increase (23 [44.2%]; 9 [22%]), AST increase (21 [40.4%]; 12 [29.3%]), fatigue and nausea (17 [32.7%]; 19 [46.3%] each). The most common grade ≥3 TEAEs among patients with glioma were seizure (4 [7.7%]), increased ALT (3 [5.8%]) and increased AST (2 [3.8%]). 5 dose-limiting toxicities of elevated transaminases (grade ≥2) occurred in the ≥100 mg cohort. Other TEAEs are listed.

The FDA has updated the product information of Treanda (bendamustine hydrochloride; DNA alkylating agent) to include a warning about progressive multifocal leukoencephalopathy (PML; including fatal events) in patients treated with bendamustine alone or in combination with rituximab or obinutuzumab; and secondary malignancies and non-melanoma skin cancer (including basal cell carcinoma and squamous cell carcinoma). PML and non-melanoma skin cancer have also been added as adverse reactions reported postmarketing. Regulatory Agency Communication

Conclusions from a Periodic Safety Update Report on Tysabri (natalizumab; integrin, alpha 4 subunit antagonist). Based on data from clinical and non-clinical trials and postmarketing reports, a causal relationship between natalizumab and thrombocytopenia and immune (or idiopathic) thrombocytopenic purpura is considered at least a reasonable possibility. The product information will be updated accordingly. Regulatory Agency Communication

Expanded access program of Zyesami (aviptadil; VPAC1/2 receptor agonist) in 240 ICU patients with critical COVID-19 and respiratory failure who were ineligible for the Zyesami phase IIb/III clinical trial. Treatment-related adverse events (AEs) included diarrhea, hypotension (5% each). Other AEs were tachycardia and flushing. [Data from an NRx Pharmaceuticals communication announcing positive data from its Zyesami expanded access protocol] Company Communication

First-in-human study of JPI-547 (PARP-1/2 and tankyrase-1/2 inhibitor; 50-200 mg PO qd) in 22 patients with advanced solid tumors. The most frequent treatment-related adverse events (>20% patients) were anemia, thrombocytopenia and neutropenia.  Congress Alert

Phase III study of NVX-CoV2373 (SARS-CoV-2 proteins-directed immunity inducer) in 29,960 healthy subjects. The most common local symptoms were injection-site pain and tenderness. The most common systemic symptoms were fatigue, headache and muscle pain. [Data from a Novavax communication announcing positive phase III results for its COVID-19 vaccine candidate] Company Communication

Phase III trial of regdanvimab (CT-P59; SARS-CoV-2 spike protein inhibitor; 40 mg/kg) for COVID-19 treatment. Mild and transient infusion-related reactions were reported. [Data from a Celltrion communication announcing positive top-line results from a phase III trial of regdanvimab for the treatment of COVID-19] Company Communication

First-in-human phase I study of TAS3681 (androgen receptor antagonist; 25-1,000 mg PO qd or 300-400 mg PO bid) in 56 patients with prostate cancer. The most common treatment-related adverse events were nausea (32 patients [57.1%]), hyperbilirubinemia (21 [37.5%]), fatigue (18 [32.1%]), vomiting (17 [30.4%]) and diarrhea (16 [28.6%]). 11 (19.6%) patients experienced QT prolongation. Congress Alert

The EMA’s PRAC has concluded that the product information of Vaxzevria (AstraZeneca COVID-19 vaccine) should be updated to include capillary leak syndrome as a side effect of unknown frequency. 6 cases have been reported to date (including 1 fatal case). Regulatory Agency Communication

First-in-human study of LVGN6051 (4-1BB activator; up to 7 mg/kg q3w), as monotherapy or in combination with pembrolizumab (PD-1 inhibitor; 200 mg q3w), in 16 patients with advanced or metastatic malignancies. No treatment-related adverse events (TRAEs) were observed in the monotherapy cohort (n = 12). The most common TRAEs of combined therapy (n = 4) were increased ALT/AST, thrombocytopenia, neutropenia, nausea and fatigue. 1 patient experienced a dose-limiting toxicity of grade 3 ALT/AST elevation. Congress Alert

First case report of central nervous system inflammatory demyelination (ID) in a 51-year-old woman with a novel frameshift variant in CTLA-4. This report provides evidence that disruption of the CTLA-4 pathway can cause ID, so caution is needed with the use of CTLA-4 immune checkpoint inhibitors in patients with a history of ID.

First-in-human phase I study assessing the tolerability of intramuscular KMRC011 (TLR5 agonist; 5-20 mcg) in 26 healthy subjects. The most common adverse events (AEs; ≥5 subjects) were injection-site reactions (mainly tenderness), pyrexia, increased C-reactive protein, myalgia and headache. Severe AEs included increased hepatic enzyme (2 events), flushing and pyrexia (1 each). KMRC011 was associated with decreased blood pressure and increased body temperature. Other AEs are listed.

First-in-human phase I study of the antibody-drug conjugate cofetuzumab pelidotin (CCK4/tubulin polymerization inhibitor; 0.2-3.7 mg/kg q3w or 2.1-3.2 mg/kg q2w) in patients with advanced solid tumors. The most common treatment-related adverse events (TRAEs) reported in the q3w dosing groups were nausea (50/112 patients [44.6%]), alopecia (46 [41.1%]), fatigue (41 [36.6%]), headache (37 [33%]), neutropenia (32 [28.6%]) and vomiting (28 [25%]). TRAEs observed in the q2w dosing groups included alopecia (17/25 [68%]), nausea (11 [44%]), fatigue and headache (10 [40%] each). Other TRAEs are listed.

Results from the phase II portion of a phase I/II study of sotorasib (KRAS G12C inhibitor; 960 mg PO qd) in 126 patients with locally advanced or metastatic KRAS p.G12C-mutated non-small-cell lung cancer. The most frequent treatment-related adverse events (TRAEs) were diarrhea (40 [31.7%] patients; 5 [4%] grade 3), nausea (24 [19%]), ALT increase (19 [15.1%]; 8 [6.3%]), AST increase (19 [15.1%]; 7 [5.6%]) and fatigue (14 [11.1%]). The most common TRAEs that led to dose modification were diarrhea, AST increase (10 [7.9%] each), ALT increase (9 [7.1%]), increase in blood alkaline phosphatase and nausea (3 [2.4%] each). Other TRAEs are listed.

First-in-human phase I/II study of CPI-0209 (EZH2 inhibitor; 50-375 mg qd) in 40 patients with advanced malignancies. The most common treatment-related adverse events (AEs; > 2 patients) were anemia, diarrhea, nausea, vomiting, fatigue, thrombocytopenia/decreased platelet count, dysgeusia and alopecia. Grade 3-4 AEs included thrombocytopenia, anemia, abdominal pain, pneumonia, increased amylase, AST and alkaline phosphatase levels, pulmonary embolism and back pain (2 patients [5%] each). Other AEs are listed. Congress Alert

Phase I study of KD033 (bispecific PD-L1/IL-15 inhibitor; 3-600 mcg/kg IV q2w) in 9 patients with advanced solid tumors. The most common treatment-related adverse events (TRAEs) were chills (9), fatigue, pyrexia (5 each), peripheral edema and hypercalcemia (3 each). Grade ≥3 TRAEs were decreased lymphocyte count (4) and edema peripheral (1). Other TRAEs are listed. Congress Alert

First-in-human phase I study of the human antibody SRF-388 (IL-27 inhibitor; 0.003-20 mg/kg) in 12 patients with advanced solid tumors. Treatment-related adverse events were fatigue (2 patients), nausea, excess salivation, cough and hyperthyroidism (1 each). Congress Alert

Tembexa carries a black box warning for increased mortality when used for longer durations than at the recommended dosage. [Data from FDA approved drug report for Tembexa (brincidofovir; viral DNA polymerase inhibitor)] Regulatory Agency Communication

First-in-human phase I trial of WX390 (PI3K/mTOR inhibitor; 0.1-1.4 mg PO qd) in 25 patients with advanced lymphoma or solid tumors. The most common treatment-related adverse events (TRAEs) were hyperglycemia (80% patients), increased creatinine (44%), proteinuria, hypophosphatemia (40% each), anemia (33.3%), thrombocytopenia (29.2%) and increased AST (25%). 1 dose-limiting toxicity of diabetic ketoacidosis combined with grade 3 hyperglycemia was reported in the 1.4 mg cohort. Grade ≥3 TRAEs are listed. Congress Alert

Preliminary results from a first-in-human phase Ia study of CBP-1008 (folate receptor alpha/TRPV6 ligand and tubulin polymerization inhibitor; 0.015-0.18 mg/kg) in patients with advanced solid malignancies. The most frequent drug-related adverse events were fever (83.3% patients), increased AST (72.2%; 5.6% grade 3-4), neutropenia (66.7%; 38.9%), leukopenia (66.7%; 27.8%) and hypohemoglobinemia (55.6%; 5.6%). Dose-limiting toxicities are listed. Congress Alert

First-in-human study of YL-13027 (ALK5 inhibitor; 60, 120, 180, 240 or 300 mg PO bid) in 13 patients with advanced solid tumors. The most common treatment-related adverse events were gamma-glutamyltransferase increase (38.5% patients all grades; 7.7% grade ≥3), hemoglobin decrease (38.5%; 0%), blood alkaline phosphatase increase (23.1%; 7.7%), aspartate aminotransferase increase and blood phosphorus decrease (23.1%; 0% each).  Congress Alert

First-in-human study of YH001 (CTLA-4 inhibitor; 0.05-6 mg/kg IV) in combination with toripalimab (PD-1 inhibitor; 240 mg q3w) in 10 patients with advanced solid tumors. Treatment-related adverse events were pruritic rash (2 patients; grade [G] 1 at 0.1 mg/kg), fatigue (2 G1 at 0.3 mg/kg), maculopapular rash (1 G2 at 0.05 mg/kg), hypothyroidism (1 G2 at 0.1 mg/kg), rash, macular rash, hyperthyroidism (1 G1 at 0.1 mg/kg each), hypotension, dry skin and pruritus (1 G1 at 0.05 mg/kg each). Congress Alert

Wegovy carries a black box warning for the risk of thyroid C-cell tumors including medullary thyroid carcinoma in rodents. [Data from FDA approved drug report for Wegovy (semaglutide; GLP-1 receptor agonist)] Regulatory Agency Communication

The FDA has updated the product information of Reyvow (lasmiditan; 5-HT1F receptor agonist) to include feeling hot and feeling cold as adverse reactions identified during clinical trials. Regulatory Agency Communication

New Zealand’s Medsafe has issued a safety review on adverse events (AEs) following immunization with Pfizer-BioNTech COVID-19 vaccine. The most common AEs reported to the Centre for Adverse Reactions Monitoring (CARM) were headache (936 reports), dizziness (770), injection-site pain (659), nausea (616), lethargy (523), fever (425), flu-like illness (381), musculoskeletal pain (251), feeling hot and cold (181) and muscle pain (159). 12 serious AEs have been recently reported to the CARM, which included allergic reactions (4), anaphylaxis (2), chest discomfort, Bell’s palsy, seizure, myocarditis, vertigo and hearing loss (1 each). A novel safety signal following COVID-19 vaccination was identified: herpes zoster. 7 reports of herpes zoster have been identified in New Zealander subjects receiving Pfizer-BioNTech COVID-19 vaccine. Other AEs are listed. Regulatory Agency Communication

First-in-human phase I study of the bispecific antibody HX009 (CD47/PD-1 inhibitor; 0.1-7.5 mg/kg q2w) in 21 patients with advanced malignancies. Treatment-related adverse events included nausea, rash, vomiting, decreased appetite (2 patients each), serious pneumonitis and anemia (1 each). Congress Alert

Phase II study of HLX10 (PD-1 inhibitor; 4.5 mg/kg q3w) plus albumin-bound paclitaxel (260 mg/m2 q3w) in 21 patients with advanced cervical cancer. The most common grade ≥3 treatment-emergent adverse events were decreased neutrophil count (7 [33.3%] patients), decreased white blood cell count (6 [28.6%]) and anemia (4 [19%]). 1 patient died from multiple organ dysfunction syndrome (considered possibly related to treatment). Congress Alert

Phase II study of famitinib (tyrosine kinase inhibitor; 20 mg) in combination with camrelizumab (200 mg) and nab-paclitaxel (100 mg/m2) in 48 patients with breast cancer. Grade 3/4 adverse events were neutropenia (33.3%), anemia, febrile neutropenia (10.4% each), thrombocytopenia (8.3%), hypertension, hypothyroidism (4.2% each), proteinuria, septicemia and immune-related myocarditis (2.1% each). Congress Alert

The special warnings and precautions for use section of the EMA EPAR for Drovelis indicates that it may cause venous thromboembolism (VTE; which may be fatal) including deep venous thrombosis and pulmonary embolism; and unscheduled and irregular bleeding or spotting with absence of withdrawal bleeding. Combined hormonal contraceptives (including ethinylestradiol-containing products) are associated with VTE including rare thrombosis in other blood vessels such as hepatic, mesenteric, renal or retinal veins and arteries; arterial thromboembolism including myocardial infarction and cerebrovascular accident; and increased risk of tumors such as cervical cancer, breast cancer, and benign and malignant liver tumor. Other adverse events are listed, including those reported with drospirenone, ethinylestradiol and drug combinations. [Data from EMA European public assessment report for Drovelis (drospirenone/estetrol)] Regulatory Agency Communication

The warnings and precautions section of the FDA approved drug report for Aduhelm indicates that it may cause amyloid-related imaging abnormalities-edema including brain edema or sulcal effusions and abnormalities-hemosiderin deposition including microhemorrhage and superficial siderosis, all of them can be severe; and hypersensitivity reactions including angioedema and urticaria. [Data from FDA approved drug report for Aduhelm (aducanumab-avwa; beta-amyloid aggregation inhibitor)] Regulatory Agency Communication

Bluebird bio communication announcing that the FDA has lifted the clinical holds on its phase I/II and phase III studies of bb1111 (hemoglobin subunit beta gene therapy) for sickle cell disease (SCD) and phase III studies of betibeglogene autotemcel for beta-thalassemia. Upon further assessment, the treating investigator concluded that the case of myelodysplastic syndrome reported in the phase I/II study of bb1111 for SCD on April was actually a case of transfusion-dependent anemia. Company Communication