1 INDICATIONS AND USAGE REVTORPYK is indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting [see Dosage and Administration (2.1) and Clinical Studies (14) ] . REVTORPYK is a kinase inhibitor indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting. (1)

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied REVTORPYK for injection is a white to off-white lyophilized powder supplied as: Carton Content NDC One 180 mg single-dose vial NDC 84577-751-01 Storage and Handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted 15°C to 30°C (59°F to 86°F). Store vial in original carton until time of reconstitution.

2 DOSAGE AND ADMINISTRATION Recommended dosage : 180 mg intravenously as a 30-minute infusion once weekly on Days 1, 8, and 15 of a 28-day cycle ( 2.2 ) Prophylactically initiate steroid-containing alcohol-free mouthwash to reduce the incidence and severity of stomatitis. ( 2.3 ) See Full Prescribing Information for dosage modifications due to adverse reactions. ( 2.4 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.5 ) 2.1 Patient Selection Select patients for treatment of HR-positive, HER2-negative locally advanced or metastatic breast cancer with REVTORPYK based on the absence of detected PIK3CA mutations in breast cancer [see Clinical Studies (14) ] . An FDA-authorized test for the determination of PIK3CA mutation status in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer is not available. 2.2 Recommended Dosage and Administration The recommended dosage of REVTORPYK is 180 mg as an intravenous infusion over 30 minutes once weekly on Days 1, 8, and 15 of every 28-day cycle, in combination with fulvestrant, with or without palbociclib, until disease progression or unacceptable toxicity. If a planned dose is delayed or missed, administer as soon as possible thereafter. Do not wait until the next planned dose in the cycle. Adjust the timing of the subsequent dose to maintain the 3 weeks on followed by 1 week off schedule. Refer to the Prescribing Information for fulvestrant and palbociclib administered in combination with REVTORPYK for additional dosing information. 2.3 Stomatitis Prophylaxis Initiate steroid-containing alcohol-free mouthwash when starting REVTORPYK. Continue to administer steroid-containing alcohol-free mouthwash 4 times daily for the first 8 weeks of treatment and longer if needed [see Warnings and Precautions (5.1) and Patient Counseling Information (17) ] . 2.4 Dosage Modifications for Adverse Reactions The recommended dosage reduction levels for adverse reactions are listed in Table 1. Table 1: Recommended Dosage Reductions of REVTORPYK for Adverse Reactions Dose Reductions Recommended Dose First 150 mg Second 130 mg Permanently discontinue REVTORPYK in patients who are unable to tolerate 130 mg intravenously once weekly on Days 1, 8, and 15 of every 28-day cycle. The recommended dosage modifications for adverse reactions are described in Table 2. Table 2: Recommended Dosage Modifications of REVTORPYK for Adverse Reactions Abbreviations: FBG, fasting blood glucose; FPG, fasting plasma glucose; ULN, upper limit of normal. Adverse Reaction Severity Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dosage Modification Stomatitis [see Warnings and Precautions (5.1) ] Grade 3 Withhold REVTORPYK until recovery to Grade ≤2. Resume at next lower dose. Grade 4 Permanently discontinue REVTORPYK. Hematologic Toxicities [see Adverse Reactions (6.1) ] Grade 4 Withhold REVTORPYK until recovery to Grade ≤2. Resume at next lower dose. Dermatologic Adverse Reactions [see Warnings and Precautions (5.2) ] Grade 3 rash (both maculopapular and acneiform) Withhold REVTORPYK until recovery to Grade ≤1. Resume at next lower dose. For recurrent Grade 3, permanently discontinue REVTORPYK. Grade 4 rash (acneiform) Permanently discontinue REVTORPYK. Any Grade of Stevens-Johnson Syndrome (SJS)/‌Toxic Epidermal Necrolysis (TEN) or other SJS/TEN-like severe skin reactions Permanently discontinue REVTORPYK. Hyperglycemia (Fasting Glucose [FG]) [see Warnings and Precautions (5.3) ] FG levels (FPG or FBG) > ULN-160 mg/dL (>ULN-8.9 mmol/L) No adjustment of REVTORPYK required. Initiate dietary modifications and ensure adequate hydration. Consider initiating or intensifying oral anti-hyperglycemic treatment as clinically indicated. FG levels 161-250 mg/dL (9-13.9 mmol/L) No adjustment of REVTORPYK required. Initiate dietary modifications, ensure adequate hydration, and consider initiation or intensify anti-hyperglycemic treatment. Consider consultation with a healthcare professional experienced in the treatment of hyperglycemia. 251-500 mg/dL (14-27.8 mmol/L) Ensure adequate hydration. Retest glucose: If glucose remains >250 mg/dL, initiate or intensify anti-hyperglycemic treatment and withhold REVTORPYK. If glucose is <250 mg/dL (<13.9 mmol/L), initiate REVTORPYK at the same dose. Consider consultation with a healthcare professional experienced in the treatment of hyperglycemia. >500 mg/dL (>27.8 mmol/L) Withhold REVTORPYK Initiate or intensify anti-hyperglycemic treatment. Ensure adequate hydration. Consider consultation with a healthcare professional experienced in the treatment of hyperglycemia. If glucose decreases to <250 mg/dL (<13.9 mmol/L), resume REVTORPYK at next lower dose. For recurrent increase in glucose >500 mg/dL, permanently discontinue REVTORPYK. Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 2 If Grade 2 persists for longer than 3 weeks, withhold REVTORPYK until recovery to Grade ≤1, then resume treatment at next lower dose. Grade 3 Withhold REVTORPYK until recovery to Grade ≤1. Resume at next lower dose. Grade 4 Permanently discontinue REVTORPYK. 2.5 Preparation and Administration Reconstitute and further dilute REVTORPYK prior to intravenous infusion. Use appropriate aseptic technique. Reconstitution Add 20 mL of Sterile Water for Injection or 5% Dextrose Injection to the REVTORPYK vial. Swirl the vial until completely dissolved for up to 5 minutes. Minor foaming and opalescence may be observed. If not used immediately, store the reconstituted solution in the vial for up to 4 hours at room temperature at 20°C to 25°C (68°F to 77°F). Do not freeze or refrigerate. REVTORPYK does not contain a preservative. Discard unused reconstituted REVTORPYK vial after 4 hours. DO NOT use common chloride-containing infusion solutions (for example: normal saline, Ringer’s solution, Lactated Ringer’s solution). Dilution Withdraw the appropriate volume of the reconstituted solution from the REVTORPYK vial (See Table 3) using a sterile syringe. Inspect visually for particulate matter and discoloration prior to administration. The solution should be free of visible particulates, be clear (minor opalescence is acceptable) and colorless to pale yellow. Discard the vial if particles or discoloration are observed. Table 3: Volume to Withdraw from Reconstituted Vial Based on Dose Dose Volume of Reconstituted REVTORPYK 180 mg 20 mL 150 mg 17 mL 130 mg 14 mL Dilute the reconstituted REVTORPYK in an infusion bag containing 250 mL of 5% Dextrose Injection. Gently invert the infusion bag to thoroughly mix the solution. Do not shake. If not used immediately, store the diluted REVTORPYK infusion solution at room temperature at 20°C to 25°C (68°F to 77°F) for up to 24 hours. Do not freeze or refrigerate. Discard any unused portion left in the vial. Administration Flush the intravenous line with 5% Dextrose Injection before REVTORPYK administration. Administer REVTORPYK by intravenous infusion over 30 minutes through a dedicated infusion line equipped with a sterile, non-pyrogenic, in-line or add-on polyether sulfone filter (0.2- or 0.22-micron pore size) and catheter. DO NOT administer any chloride-containing solutions (e.g., Sodium Chloride for Injection, Ringer’s Injection, Lactated Ringer’s Injection) or other medications concomitantly via the same intravenous line. Upon completion of the infusion, flush the intravenous line with 5% Dextrose Injection. Discard any unused portions left in the infusion set.

4 CONTRAINDICATIONS None. None. ( 4 )

5 WARNINGS AND PRECAUTIONS Stomatitis: REVTORPYK can cause severe stomatitis, including mouth ulcers. Initiate steroid-containing alcohol-free mouthwash prior to starting treatment. Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity. ( 2.3 , 2.4 , 5.1 ) Dermatologic Adverse Reactions: REVTORPYK can cause severe rash. Monitor patients for rash and infectious sequelae. Instruct patients to limit sun exposure during REVTORPYK treatment. Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity. ( 2.4 , 5.2 ) Hyperglycemia: REVTORPYK can cause severe hyperglycemia. Evaluate blood glucose levels and hemoglobin A1c prior to starting and at regular intervals during treatment. Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity. ( 2.4 , 5.3 ) Embryo-Fetal Toxicity: REVTORPYK can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. Refer to the Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information. ( 5.4 , 8.1 , 8.3 ) 5.1 Stomatitis REVTORPYK can cause severe stomatitis, including ulcers and oral mucositis. In Study 1 of VIKTORIA-1, stomatitis occurred in 72% of patients treated with REVTORPYK with fulvestrant and palbociclib, including Grade 3 events in 22% of patients. Prophylactic steroid-containing alcohol-free mouthwash was required for a minimum of 8 weeks. The median time to onset was 7 days (range: 1 to 457 days). Stomatitis led to REVTORPYK dose reduction in 19% and permanent discontinuation in 3.8% of patients. Stomatitis occurred in 58% of patients treated with REVTORPYK with fulvestrant, including Grade 3 events in 12% of patients. The median time to onset was 4 days (range: 1 to 524 days). Stomatitis led to REVTORPYK dose reduction in 9% and permanent discontinuation in 1.5% of patients. Prophylactically initiate steroid-containing alcohol-free mouthwash to reduce the incidence and severity of stomatitis [see Dosage and Administration (2.3) ] . If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated. Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity [see Dosage and Administration (2.4) ] . 5.2 Dermatologic Adverse Reactions REVTORPYK can cause severe rash. In Study 1 of VIKTORIA-1, rash occurred in 30% of patients treated with REVTORPYK in combination with fulvestrant and palbociclib, including Grade 3 events in 6% of patients. The median time to onset was 21 days (range: 3 to 260 days) after starting REVTORPYK. Rash led to REVTORPYK dose reduction in 5% and permanent discontinuation in 0.8% of patients. Rash occurred in 40% of patients treated with REVTORPYK in combination with fulvestrant, including Grade 3 events in 5% of patients. Rash led to REVTORPYK dose reduction in 6% and permanent discontinuation in 0.8% of patients. The median time to onset was 31.5 days (range: 2 to 407 days) after starting REVTORPYK. Monitor patients receiving REVTORPYK for rash and infectious sequelae. Instruct patients to limit sun exposure during REVTORPYK treatment. Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity [see Dosage and Administration (2.4) ] . 5.3 Hyperglycemia Severe hyperglycemia can occur in patients treated with REVTORPYK. Hyperglycemia is associated with drugs that inhibit the PI3K/AKT/mTOR pathway. In Study 1 of VIKTORIA-1, increased fasting glucose (FG) from baseline occurred in 46% of patients treated with REVTORPYK in combination with fulvestrant and palbociclib, including Grade 1 (FG >ULN to 160 mg/dL) in 36% of patients, Grade 2 (FG >160 to 250 mg/dL) in 8% of patients and Grade 3 (FG >250 to 500 mg/dL) in 0.9% of patients. Increased fasting glucose from baseline occurred in 57% of patients treated with REVTORPYK in combination with fulvestrant, including Grade 1 in 44% of patients, Grade 2 in 11% of patients and Grade 3 in 1.8% of patients. The safety of REVTORPYK in patients with Type 1 or uncontrolled Type 2 diabetes mellitus has not been established as these patients were excluded from Study 1 of VIKTORIA-1 [see Clinical Studies (14) ] . Before initiating treatment with REVTORPYK, test fasting glucose levels (FPG or FBG), HbA1c levels, and optimize fasting glucose. Achieve optimal glucose control before starting each REVTORPYK infusion [see Dosage and Administration (2.4) ] . Manage hyperglycemia with anti-hyperglycemic medications. Patients with a history of well-controlled Type 2 diabetes mellitus may require intensified anti-hyperglycemic treatment and close monitoring of FG levels. Consider consultation with a healthcare professional experienced in the treatment of hyperglycemia. Initiate at-home glucose monitoring for patients with HbA1c level >6.4%. Advise patients of the signs and symptoms of hyperglycemia and counsel patients on lifestyle changes. Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity [see Dosage and Administration (2.4) ] . 5.4 Embryo-Fetal Toxicity Based on its mechanism of action, REVTORPYK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . Inhibition of PI3K and mTOR pathways have been associated with adverse embryo-fetal growth and lethality in animals. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with REVTORPYK and for 2 weeks after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with REVTORPYK and for 2 weeks after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )] . REVTORPYK is used in combination with fulvestrant, with or without palbociclib. Refer to the Prescribing Information of fulvestrant and palbociclib for pregnancy and contraception information. When REVTORPYK is used in combination, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Stomatitis Inform patients of the risk of stomatitis. Advise patients to contact their healthcare provider if they experience any symptoms (e.g., painful redness, swelling, or sores in the mouth). Inform patients to use steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct patients not to eat or drink for at least 1 hour after administration of the steroid-containing mouthwash [see Warnings and Precautions (5.1) ] . Dermatologic Adverse Reactions Inform patients of the risks of dermatologic adverse reactions, including rash. Advise patients to limit sun exposure during treatment. Advise patients to contact their healthcare provider immediately if they develop a new rash [see Warnings and Precautions (5.2) ] . Hyperglycemia Inform patients of the risks of hyperglycemia and the need for monitoring of fasting blood glucose and HbA1c periodically during treatment. Advise patients to contact their healthcare provider immediately for signs and symptoms of hyperglycemia (e.g., excessive thirst, urinating more often, blurred vision, confusion, difficulty breathing, or increased appetite with weight loss) [see Warnings and Precautions (5.3) ] . Embryo-Fetal Toxicity Inform pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with REVTORPYK and for 2 weeks after the last dose [see Use in Specific Populations (8.3) ] . Advise male patients with female partners of reproductive potential to use effective contraception during treatment with REVTORPYK and for 2 weeks after the last dose [see Use in Specific Populations (8.3) ] . Refer to the Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information. When used in combination with REVTORPYK, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products. Lactation Advise women not to breastfeed during treatment with REVTORPYK and for 2 weeks after the last dose [see Use in Specific Populations (8.2) ] . Refer to the Prescribing Information of palbociclib and fulvestrant for lactation information. When used in combination, advise patients not to breastfeed during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products. Infertility Advise females and males of reproductive potential that REVTORPYK may impair fertility [see Use in Specific Populations (8.3) ] . Refer to the Prescribing Information of palbociclib and fulvestrant for infertility information. This product's labeling may have been updated. For full prescribing information, please visit www.celcuity.com . Manufactured for: Celcuity Inc. 2800 Campus Dr, Suite 140 Minneapolis, MN 55441

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies have not been conducted with gedatolisib. Mutagenesis Gedatolisib was not mutagenic in vitro in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro human lymphocyte chromosomal aberration assay. Gedatolisib was not genotoxic in an in vivo rat bone marrow micronucleus assay. Impairment of Fertility Fertility studies with gedatolisib have not been conducted. In repeated-dose toxicity studies, gedatolisib was administered intravenously once weekly on a 3 weeks on/1 week off schedule for 3 months in rats and dogs. Degeneration/atrophy of seminiferous tubules in testes was observed in male rats and dogs at ≥ 5 mg/kg and 0.5 mg/kg, respectively, and atrophy of prostate was observed in male rats at ≥ 1 mg/kg. In female rats, atrophy in the vagina and uterus was observed at ≥ 5 mg/kg. All findings occurred at exposures ≤ 0.2 times the human AUC at the recommended dose. Findings in males and females were reversible following a 12-week recovery period.

8.1 Pregnancy Risk Summary REVTORPYK is used in combination with fulvestrant, with or without palbociclib. Refer to the Prescribing Information for fulvestrant and palbociclib for pregnancy information. When used in combination with REVTORPYK, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products. Based on its mechanism of action, REVTORPYK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data in pregnant women to inform the drug-associated risk. Animal reproductive toxicity studies have not been conducted with REVTORPYK. Inhibition of PI3K and mTOR pathways have been associated with adverse embryo-fetal growth and lethality in animals ( see Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data PIK3CA knockout mice experienced developmental delay at embryonic day 9.5 and mortality between embryonic day 9.5 and 10.5. mTOR knockout mice experienced early lethality by embryonic day 7.5. In both animal models, early embryonic death was a result of impaired cell proliferation and structural development.

8.4 Pediatric Use The safety and efficacy of REVTORPYK in pediatric patients have not been established.

8.5 Geriatric Use Of 260 patients who received REVTORPYK, 55 patients (21%) were ≥65 and <75 years of age and 17 patients (6.5%) were ≥75 years of age [see Clinical Studies (14) ] . In patients treated with REVTORPYK in combination with fulvestrant and palbociclib, the incidence of Grade ≥3 stomatitis and rash was higher in patients ≥65 years of age (37% and 11%, respectively) compared to younger patients (16% and 4.3%, respectively). In patients treated with REVTORPYK in combination with fulvestrant, the incidence of Grade ≥3 stomatitis and rash was higher in patients ≥65 years of age (18% and 12%, respectively) compared to younger patients (10% and 3.1%, respectively). No overall differences in effectiveness of REVTORPYK were observed between patients ≥65 years of age and younger patients.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Stomatitis [see Warnings and Precautions (5.1) ] Dermatologic adverse reactions [see Warnings and Precautions (5.2) ] Hyperglycemia [see Warnings and Precautions (5.3) ] The most common (≥20%) adverse reactions, including laboratory abnormalities when given in combination with fulvestrant and palbociclib were decreased white blood cells, decreased neutrophils, decreased hemoglobin, decreased lymphocytes, stomatitis, nausea, decreased platelets, increased fasting glucose, fatigue, vomiting, rash, constipation, diarrhea, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), musculoskeletal pain, decreased sodium, and increased eosinophils. ( 6.1 ) The most common (≥20%) adverse reactions, including laboratory abnormalities when given in combination with fulvestrant were stomatitis, increased fasting glucose, increased eosinophils, decreased hemoglobin, nausea, rash, increased ALT, fatigue, musculoskeletal pain, decreased lymphocytes, vomiting, increased AST, pruritus, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Celcuity Inc. at 1-877-4-CELCUITY (1-877-423-5284) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of REVTORPYK was evaluated in 383 adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer without a detectable PIK3CA mutation in Study 1 of VIKTORIA-1 [see Clinical Studies (14) ] . Patients received either Arm A: REVTORPYK 180 mg intravenously once weekly for 3 weeks on followed by 1 week off (Days 1, 8, 15 for each 28-day cycle) in combination with fulvestrant 500 mg intramuscularly on cycle 1 Days 1 and 15, and then at Day 1 of each subsequent 28-day cycle and palbociclib 125 mg orally once daily for 21 days followed by 7 days off treatment for each 28-day cycle (n = 130); or Arm B: REVTORPYK in combination with fulvestrant (n = 130); or Arm C: fulvestrant alone (n = 123). The dose, route of administration, and frequency of each drug in Arms B and C were the same as Arm A. The median duration of exposure for REVTORPYK plus fulvestrant and palbociclib was 6.2 months (range: 0.5 to 25 months) and 5.7 months (range: 0 to 26 months) for REVTORPYK plus fulvestrant. REVTORPYK in Combination with Fulvestrant and Palbociclib Serious adverse reactions occurred in 25% of patients who received REVTORPYK in combination with fulvestrant and palbociclib. Serious adverse reactions in ≥1% of patients included pneumonia (3.8%), thrombosis (3.8%), and stomatitis (1.5%). Fatal adverse reactions occurred in 2.3% of patients who received REVTORPYK in combination with fulvestrant and palbociclib, including (0.8% each) pneumonia, multiorgan failure, and hepatic failure. Permanent discontinuation of REVTORPYK due to an adverse reaction occurred in 12% of patients receiving REVTORPYK in combination with fulvestrant and palbociclib. Adverse reactions that resulted in permanent discontinuation of REVTORPYK were stomatitis, nausea, rash, pneumonitis, diplopia, hypertension, vomiting, breast ulceration, and squamous cell carcinoma of the lung. Dosage interruptions of REVTORPYK due to an adverse reaction occurred in 64% of patients receiving REVTORPYK in combination with fulvestrant and palbociclib. Adverse reactions which required dosage interruption of REVTORPYK in ≥2% of patients included neutropenia, stomatitis, decreased neutrophil count, fatigue, anemia, leukopenia, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), pyrexia, rash, thrombosis, pneumonia, diarrhea, hyperglycemia, thrombocytopenia, upper respiratory tract infection, pruritus, and urinary tract infection. Dose reductions of REVTORPYK due to an adverse reaction occurred in 41% of patients receiving REVTORPYK in combination with fulvestrant and palbociclib. Adverse reactions which required dose reduction of REVTORPYK in ≥2% of patients included stomatitis, neutropenia, rash, nausea, increased AST, and increased ALT. The most common (≥20%) adverse reactions, including laboratory abnormalities, in the REVTORPYK in combination with fulvestrant and palbociclib arm were decreased white blood cell, decreased neutrophils, decreased hemoglobin, decreased lymphocytes, stomatitis, nausea, decreased platelets, increased fasting glucose, fatigue, vomiting, rash, constipation, diarrhea, increased ALT, increased AST, musculoskeletal pain, decreased sodium, and increased eosinophils. REVTORPYK in Combination with Fulvestrant Serious adverse reactions occurred in 19% of patients who received REVTORPYK in combination with fulvestrant. Serious adverse reactions in ≥1% of patients included pneumonia (3.8%), thrombosis (2.3%), pleural effusion (1.5%), and pneumonitis (1.5%). Fatal adverse reactions occurred in 2.3% of patients who received REVTORPYK in combination with fulvestrant, including (0.8% each) acute respiratory failure, bronchopulmonary hemorrhage, and cardiac arrest. Permanent discontinuation of REVTORPYK due to an adverse reaction occurred in 9% of patients receiving REVTORPYK in combination with fulvestrant. Adverse reactions that resulted in permanent discontinuation of REVTORPYK were stomatitis, nausea, rash, pneumonitis, acute respiratory failure, myocarditis, angina pectoris, fatigue, infusion-related reaction, peripheral neuropathy, and oral pain. Dosage interruptions of REVTORPYK due to an adverse reaction occurred in 37% of patients receiving REVTORPYK in combination with fulvestrant. Adverse reactions which required dosage interruption of REVTORPYK in ≥2% of patients included fatigue, increased AST, increased ALT, stomatitis, pneumonia, pyrexia, and diarrhea. Dose reductions of REVTORPYK due to an adverse reaction occurred in 22% of patients receiving REVTORPYK in combination with fulvestrant. Adverse reactions which required dose reduction of REVTORPYK in ≥2% of patients included stomatitis, rash, and nausea. The most common (≥20%) adverse reactions, including laboratory abnormalities, in the REVTORPYK in combination with fulvestrant arm were stomatitis, increased fasting glucose, increased eosinophils, decreased hemoglobin, nausea, rash, increased ALT, fatigue, musculoskeletal pain, decreased lymphocytes, vomiting, increased AST, pruritus, and diarrhea. Tables 4 and 5 summarize the adverse reactions and laboratory abnormalities in Study 1 of VIKTORIA-1, respectively. Table 4: Adverse Reactions (≥10%) in Patients Who Received REVTORPYK plus Fulvestrant and Palbociclib in Study 1 of VIKTORIA-1 Grading according to CTCAE 5.0. N=number of patients Adverse Reaction REVTORPYK + Fulvestrant + Palbociclib (N=130) REVTORPYK + Fulvestrant (N=130) Fulvestrant (N=123) All Grades Grade 3 or 4 No Grade 4 events were reported. All Grades Grade 3 or 4 All Grades Grade 3 or 4 % % % % % % Gastrointestinal Disorders Stomatitis Includes multiple related terms. 72 22 58 12 2.4 0 Nausea 51 3.8 44 0.8 13 0.8 Vomiting 35 1.5 24 0 4.1 0 Diarrhea 26 1.5 20 1.5 4.9 0 Constipation 26 0 16 0 3.3 0 Abdominal pain 13 0 9 0 8 4.1 General Disorders and Administration Site Conditions Fatigue 43 2.3 34 0.8 13 0.8 Pyrexia 14 0 10 0 1.6 0 Mucosal dryness 11 0 10 0 1.6 0 Skin and Subcutaneous Tissue Disorders Rash 30 6 40 5 0 0 Pruritus 19 0.8 22 0 1.6 0 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain 24 0.8 26 3.1 24 2.4 Nervous System Disorders Dysgeusia 19 0 17 0 0.8 0 Dizziness 10 0 9 0 3.3 0 Metabolism and nutrition disorder Decreased appetite 19 0.8 11 0.8 4.1 0.8 Infections and Infestations Urinary Tract Infection 13 0 15 0 4.1 0 Respiratory, Thoracic and Mediastinal Disorders Cough 11 0 18 0 7 0 Vascular Disorders Thrombosis 10 3.1 3.1 2.3 0 0 Table 5: Select Laboratory Abnormalities (≥10%) in Patients Who Received REVTORPYK plus Fulvestrant and Palbociclib in Study 1 of VIKTORIA-1 N=number of patients; WBC = white blood cells; AST = aspartate aminotransferase; ALT = alanine aminotransferase; CPK = creatine phosphokinase; ALP = alkaline phosphatase. Laboratory Abnormality REVTORPYK + Fulvestrant + Palbociclib (N=130) REVTORPYK + Fulvestrant (N=130) Fulvestrant (N=123) All Grades Grade 3 or 4 All Grades Grade 3 or 4 All Grades Grade 3 or 4 % % % % % % Hematology WBC decreased 93 45 16 0.8 No Grade 4 events were reported. 13 0.8 Neutrophils decreased 85 65 14 1.6 10 0.8 Hemoglobin decreased 84 12 46 0.8 19 2.5 Lymphocytes decreased 73 27 25 2.6 21 5.4 Platelets decreased 49 6 5 0.8 11 0.8 Eosinophils increased 20 0 53 0 11 0 Chemistry Glucose (fasting) increased Glucose results were graded per CTCAE v4.03. 46 0.9 57 1.8 17 0 ALT increased 25 0.8 35 2.3 21 0 AST increased 24 2.4 23 3.1 18 1.7 Sodium decreased 21 1.6 16 0.8 13 1.7 Magnesium decreased 19 0 16 0 3.4 0 Potassium decreased 19 1.6 14 1.6 9 1.7 Glucose decreased 17 3.1 9 1.5 2.6 0.9 CPK increased 15 0.9 12 2.5 11 0.9 Creatinine increased 14 0.8 10 1.6 8 0.8 Serum amylase increased 14 0.8 10 2.3 9 0 ALP increased 12 0 18 0 21 1.7 Potassium increased 10 0.8 5 0 8 0.8