Keytruda

Pembrolizumab

Treatment of patients w/ unresectable or metastatic melanoma. Monotherapy for the adjuvant treatment of adult & ped patients ≥12 yr w/ Stage IIB, IIC, or III melanoma following complete resection. In combination w/ pemetrexed & platinum chemotherapy for the 1st-line treatment of patients w/ metastatic nonsquamous NSCLC, w/o EGFR or ALK genomic tumor aberrations. In combination w/ carboplatin & either paclitaxel or paclitaxel protein-bound for the 1st-line treatment of patients w/ metastatic squamous NSCLC. Single agent for the 1st-line treatment of patients w/ NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by a validated test, w/o EGFR or ALK genomic tumor aberrations & is: Stage III where patients are not candidates for surgical resection or definitive chemoradiation; or metastatic. Single agent for the treatment of patients w/ metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by a validated test, w/ disease progression on or after platinum-containing chemotherapy. Patients w/ EGFR or ALK genomic tumor aberrations should have disease progression on approved therapy for these aberrations prior to receiving Keytruda. Treatment of patients w/ locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy & whose tumors express PD-L1 [Combined Positive Score (CPS) ≥10] as determined by a validated test, or ineligible for any platinum-containing chemotherapy regardless of PD-L1 status. Treatment of patients w/ locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or w/in 12 mth of neoadjuvant or adjuvant treatment w/ platinum-containing chemotherapy. Treatment of patients w/ BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) w/ carcinoma in situ (CIS) w/ or w/o papillary tumors who are ineligible for or have elected not to undergo cystectomy. Monotherapy for the treatment of adult & ped patients ≥3 yr w/ relapsed or refractory classical Hodgkin lymphoma who have failed autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT is not a treatment option. Treatment of adult patients w/ unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR): Solid tumors that have progressed following prior treatment & have no satisfactory alternative treatment options; or CRC that has progressed following treatment w/ a fluoropyrimidine, oxaliplatin, & irinotecan. In combination w/ axitinib for the 1st-line treatment of adult patients w/ advanced renal cell carcinoma (RCC). In combination w/ lenvatinib for the 1st-line treatment of adult patients w/ advanced RCC. Adjuvant treatment of patients w/ RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy & resection of metastatic lesions. In combination w/ lenvatinib for the treatment of patients w/ advanced endometrial carcinoma that is mismatch repair proficient (pMMR) as determined by a validated test or not MSI-H, who have disease progression following prior systemic therapy in any setting & are not candidates for curative surgery or radiation. In combination w/ platinum & fluorouracil (FU) for the 1st-line treatment of patients w/ metastatic or unresectable, recurrent head & neck squamous cell carcinoma (HNSCC). Single agent for the 1st-line treatment of patients w/ metastatic or unresectable, recurrent HNSCC whose tumors express PD-L1 (CPS ≥1) as determined by a validated test. In combination w/ platinum- & fluoropyrimidine-based chemotherapy for the 1st-line treatment of patients w/ locally advanced or metastatic carcinoma of the esophagus or HER2 -ve gastroesophageal junction adenocarcinoma (tumour centre 1-5 cm above the gastroesophageal junction) that is not amenable to surgical resection or definitive chemoradiation. Treatment of patients w/ recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10) as determined by a validated test, w/ disease progression after 1 prior line of systemic therapy. 1st-line treatment of patients w/ unresectable or metastatic MSI-H or dMMR CRC. Treatment of adult & ped patients w/ unresectable or metastatic tumor mutational burden-high (TMB-H) (≥10 mutations/megabase) solid tumors, as determined by a validated test, that have progressed following prior treatment & have no satisfactory alternative treatment options. (Limitations of use: The safety & effectiveness of Keytuda in ped patients w/ TMB-H CNS cancers have not been established.) Treatment of patients w/ high-risk early-stage triple -ve breast cancer (TNBC) in combination w/ chemotherapy as neoadjuvant treatment, & then continued as a single agent as adjuvant treatment after surgery. In combination w/ chemotherapy for the treatment of locally recurrent unresectable or metastatic TNBC in adults whose tumors express PD-L1 w/ a CPS ≥10 & have not received prior chemotherapy for metastatic disease. In combination w/ chemotherapy, w/ or w/o bevacizumab, for the treatment of patients w/ persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by a validated test.

IV Adult Monotherapy for unresectable or metastatic melanoma 200 mg by 30-min infusion every 3 wk, or 400 mg every 6 wk, until disease progression or unacceptable toxicity. Monotherapy for adjuvant treatment of melanoma or RCC 200 mg by 30-min infusion every 3 wk, or 400 mg every 6 wk, until disease recurrence, unacceptable toxicity, or up to 12 mth. Monotherapy for NSCLC, HNSCC, cHL, locally advanced or metastatic urothelial carcinoma, MSI-H or dMMR cancer, esophageal cancer, MSI-H or dMMR CRC, or TMB-H cancer 200 mg by 30-min infusion every 3 wk, or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or up to 24 mth. Monotherapy for high-risk BCG-unresponsive NMIBC 200 mg by 30-min infusion every 3 wk, or 400 mg every 6 wk, until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 mth. Combination therapy for NSCLC, HNSCC, or esophageal cancer 200 mg by 30-min infusion every 3 wk, or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or up to 24 mth. Administer prior to chemotherapy when given on the same day. Combination therapy for cervical cancer 200 mg by 30-min infusion every 3 wk, or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or up to 24 mth (for Keytruda). Administer prior to chemotherapy w/ or w/o bevacizumab when given on the same day. Combination therapy for RCC 200 mg by 30-min infusion every 3 wk, or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or up to 24 mth (for Keytruda). Administer in combination w/ axitinib 5 mg PO bd or lenvatinib 20 mg PO once daily. Combination therapy for endometrial carcinoma 200 mg by 30-min infusion every 3 wk, or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or up to 24 mth (for Keytruda). Administer in combination w/ lenvatinib 20 mg PO once daily. Combination therapy for high-risk early-stage TNBC 200 mg by 30-min infusion every 3 wk, or 400 mg every 6 wk. Administer prior to chemotherapy when given on the same day. Neoadjuvant treatment in combination w/ chemotherapy for 24 wk (8 doses of 200 mg every 3 wk or 4 doses of 400 mg every 6 wk) or until disease progression or unacceptable toxicity, followed by adjuvant treatment w/ Keytruda as a single agent for up to 27 wk (9 doses of 200 mg every 3 wk or 5 doses of 400 mg every 6 wk) or until disease recurrence or unacceptable toxicity. Patients who experience disease progression or unacceptable toxicity related to Keytruda w/ neoadjuvant treatment in combination w/ chemotherapy should not receive adjuvant single agent Keytruda. Combination therapy for locally recurrent unresectable or metastatic TNBC 200 mg by 30-min infusion every 3 wk, or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or up to 24 mth. Administer prior to chemotherapy when given on the same day. Ped patient Monotherapy for cHL or TMB-H cancer 2 mg/kg by 30-min infusion every 3 wk, up to max 200 mg, until disease progression, unacceptable toxicity, or up to 24 mth. Monotherapy for adjuvant treatment of melanoma 2 mg/kg by 30-min infusion every 3 wk, up to max 200 mg, until disease recurrence, unacceptable toxicity, or up to 12 mth.

Immune-mediated pneumonitis: Withhold for Grade 2 pneumonitis. Permanently discontinue for Grade 3 or 4 pneumonitis. Immune-mediated colitis: Withhold for Grade 2 or 3 colitis. Permanently discontinue for Grade 4 colitis. Immune-mediated hepatitis w/o tumor involvement of the liver: Withhold if AST or ALT >3 to 8x ULN or total bilirubin >1.5 to 3x ULN. Permanently discontinue if AST or ALT >8x ULN or total bilirubin >3x ULN. In combination w/ axitinib: Withhold both Keytruda & axitinib if ALT or AST ≥3x ULN but <10x ULN w/o concurrent total bilirubin ≥2x ULN, until resolution to Grade 0 or 1. Permanently discontinue both Keytruda & axitinib if ALT or AST >3x ULN w/ concurrent total bilirubin ≥2x ULN or ALT or AST ≥10x ULN. Immune-mediated hepatitis w/ tumor involvement of the liver: Withhold if baseline AST or ALT >1 up to 3x ULN & increases to >5 up to 10x ULN or baseline AST or ALT >3 up to 5x ULN & increases to >8 up to 10x ULN. Permanently discontinue if AST or ALT >10x ULN or total bilirubin >3x ULN. Immune-mediated endocrinopathies: Withhold for Grade 3 or 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated nephritis w/ renal dysfunction: Withhold for Grade 2 or 3 increased blood creatinine. Permanently discontinue for Grade 4 increased blood creatinine. Immune-mediated exfoliative dermatologic conditions: Withhold for suspected SJS, TEN, or DRESS. Permanently discontinue for confirmed SJS, TEN, or DRESS. Myocarditis: Permanently discontinue for Grade 2, 3, or 4 myocarditis. Neurological toxicities: Withhold for Grade 2. Permanently discontinue for Grade 3 or 4 neurological toxicities. Hematologic toxicity in patients w/ cHL: Withhold for Grade 4 hematologic toxicity until resolution to Grade 0 or 1. Infusion-related reactions: Interrupt or slow infusion rate for Grade 1 or 2 infusion-related reactions. Permanently discontinue for Grade 3 or 4 infusion-related reactions. Other special precautions: Closely monitor patients who receive allogeneic hematopoietic stem cell transplantation for evidence of transplant-related complications eg, hyperacute graft versus host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, steroid-requiring febrile syndrome, & intervene promptly. Increased mortality in patients w/ multiple myeloma when Keytruda is combined w/ thalidomide analogue & dexamethasone. Modify dose of co-administered Keytruda &/or lenvatinib in case of adverse reactions. Risk of fetal harm when administered to a pregnant woman. Females of reproductive potential should use effective contraception during treatment & for 4 mth after the last dose. Do not breastfeed during treatment & for 4 mth after the last dose. Safety & effectiveness in ped patients have not been established except in indications for melanoma, cHL & TMB-H cancer.

As a single agent: Fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, hypothyroidism. In combination w/ chemotherapy: Fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, wt loss, abdominal pain, arthralgia, myalgia, insomnia. In combination w/ chemotherapy & bevacizumab: Peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, HTN, thrombocytopenia, constipation, arthralgia, vomiting, UTI, rash, leukopenia, hypothyroidism, decreased appetite. In combination w/ axitinib: Diarrhea, fatigue/asthenia, HTN, hepatotoxicity, hypothyroidism, decreased appetite, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, constipation. In combination w/ lenvatinib: Hypothyroidism, HTN, fatigue, diarrhea, musculoskeletal disorder, nausea, decreased appetite, vomiting, stomatitis, wt loss, abdominal pain, UTI, proteinuria, constipation, headache, hemorrhagic events, palmar-plantar erythrodysesthesia, dysphonia, rash, hepatotoxicity, acute kidney injury.

Targeted Cancer Therapy / Cancer Immunotherapy

L01FF02 - pembrolizumab ; Belongs to the class of PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors. Used in the treatment of cancer.

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