Unloxcyt: US approves skin cancer drug

The US Food and Drug Administration said on Friday it has approved Checkpoint Therapeutics’ drug Unloxcyt for treatment of a type of cancer on the outer layer of the skin.

Approval for the drug, which will be sold under the brand Unloxcyt, is for cutaneous squamous cell carcinoma which can be both locally advanced as well as for when it spreads into other areas of the body, the FDA said.

Unloxcyt is part of a class called PD-L1 antibody, in which the drug works by binding to a protein called programmed death-ligand 1 that helps the body’s immune system to kill cancer cells.

The approval was based on results from a study of 109 patients, in which the drug helped show an overall response rate of 47% in patients with a metastatic type of cancer and 48% in those with an advanced local form of the disease.

“Today’s FDA approval of UNLOXCYT – the first marketing approval for our company – is a significant milestone both for Checkpoint and for patients with advanced cSCC,” said James Oliviero, President and Chief Executive Officer of Checkpoint. “This approval marks Checkpoint’s transformation to a commercial-stage company, with the opportunity to compete in a U.S. market estimated to exceed $1 billion annually, where we believe UNLOXCYT offers a differentiated treatment option versus available therapies by binding to PD-L1, rather than programmed death receptor-1 (“PD-1”), to release the inhibitory effects of PD-L1 on the anti-tumor immune response. Additionally, UNLOXCYT has demonstrated the ability to induce antibody-dependent cell-mediated cytotoxicity (“ADCC”), another potential differentiating feature of the drug compared to existing marketed therapies for patients with cSCC.”

“cSCC is the second most common form of skin cancer, and those diagnosed with advanced disease that has recurred or metastasized face a poor prognosis. cSCC remains a disease with a significant need for more effective and tolerable treatment options, particularly for patients with concomitant hematological malignancies, solid organ transplant recipients, or a history of autoimmune disorders,” stated Emily Ruiz, M.D., M.P.H., Academic Director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s Hospital, Director of the High-Risk Skin Cancer Clinic at Dana Farber Cancer Center, and Associate Professor of Dermatology at Harvard Medical School. “UNLOXCYT is the first FDA-approved PD-L1–blocking antibody to demonstrate clinically meaningful objective response rates with durable responses in advanced cSCC. With its dual mechanisms of action and compelling safety profile, this promising drug will provide U.S. oncologists with an important new immunotherapy option for the treatment of cSCC.”

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (“cSCC”) is the second most common type of skin cancer in the United States, with an estimated annual incidence of approximately 1.8 million cases according to the Skin Cancer Foundation. Important risk factors for cSCC include chronic ultraviolet exposure and immunosuppressive conditions. While most cases are localized tumors amenable to curative resection, each year approximately 40,000 cases become advanced and an estimated 15,000 people in the United States die from this disease. In addition to being a life-threatening disease, cSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear. The immune-suppressed population in particular represents a challenging target in the treatment of advanced cSCC, as patients present with a more aggressive disease and with a higher risk of developing immune-related toxicities from checkpoint inhibitor treatment.

About UNLOXCYT™ (cosibelimab-ipdl)

UNLOXCYT is a human immunoglobulin G1 (“IgG1”) monoclonal antibody that binds PD-L1 and blocks the interaction between PD-L1 and its T cell receptors, PD-1 and B7.1. This interaction releases the inhibitory effects of PD-L1 on the anti-tumor immune response. UNLOXCYT has also been shown to induce ADCC.

INDICATION and IMPORANT SAFETY INFORMATION

INDICATION

UNLOXCYT (cosibelimab-ipdl) is indicated for the treatment of adults with metastatic cutaneous squamous cell carcinoma (“cSCC”) or locally advanced cSCC who are not candidates for curative surgery or curative radiation.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

• Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions. Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue, and occur at any time after starting a PD-1/PD-L1–blocking antibody, including UNLOXCYT. While immune-mediated adverse reactions usually manifest during treatment, they can also manifest after discontinuation of PD-1/PD-L1–blocking antibodies. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously.
• Monitor closely for signs and symptoms of immune-mediated adverse
  reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
• Withhold or permanently discontinue UNLOXCYT depending on the severity of the adverse reaction (see Dosage and Administration in Prescribing Information). In general, if UNLOXCYT requires interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids.

Immune-Mediated Pneumonitis

• UNLOXCYT can cause immune-mediated pneumonitis. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 1% (3/223, Grade 2) of patients receiving UNLOXCYT.

Immune-Mediated Colitis

• UNLOXCYT can cause immune-mediated colitis, which may present with diarrhea, abdominal pain, and lower gastrointestinal bleeding. Cytomegalovirus infection/reactivation has occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 0.4% (1/223, Grade 1) of patients receiving UNLOXCYT.

Immune-Mediated Hepatitis

• UNLOXCYT can cause immune-mediated hepatitis.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

• UNLOXCYT can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue UNLOXCYT depending on severity. Adrenal insufficiency occurred in 0.9% (2/223) of patients receiving UNLOXCYT, including Grade 2 in 0.4% (1/223) of patients.

Hypophysitis

• UNLOXCYT can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue UNLOXCYT depending on severity.

Thyroid Disorders

• UNLOXCYT can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue UNLOXCYT depending on severity. Hypothyroidism occurred in 10% (22/223) of patients receiving UNLOXCYT, including Grade 2 in 5% (10/223) of patients. Hyperthyroidism occurred in 5% (12/223) of patients receiving UNLOXCYT, including Grade 2 in 0.4% (1/223) of patients.

Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis

• UNLOXCYT can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue UNLOXCYT depending on severity.

Immune-Mediated Nephritis with Renal Dysfunction

• UNLOXCYT can cause immune-mediated nephritis.

Immune-Mediated Dermatologic Adverse Reactions

• UNLOXCYT can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD-1/PD-L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue UNLOXCYT depending on severity. Immune-mediated dermatologic adverse reactions occurred in 7% (15/223) of patients receiving UNLOXCYT, including Grade 3 in 0.9% (2/223) of patients and Grade 2 in 4% (9/223) of patients.

Other Immune-Mediated Adverse Reactions

• The following clinically significant immune-mediated adverse reactions occurred in <1% of the 223 patients who received UNLOXCYT or were reported with the use of other PD-1/PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.
  • Cardiac/Vascular: Myocarditis, pericarditis, vasculitis.
  • Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy.
  • Ocular: Uveitis, iritis, other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
  • Gastrointestinal: Pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis.
  • Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica.
  • Endocrine: Hypoparathyroidism.
  • Other (Hematologic/Immune): Autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.