Keytruda

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 non-squamous 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/ resectable (tumors ≥4 cm or node +ve) NSCLC in combination w/ platinum-containing chemotherapy as neoadjuvant treatment, & then continued as a single agent as adjuvant treatment after surgery. Single agent as adjuvant treatment following resection & platinum-based chemotherapy for adult patients w/ stage IB (T2a ≥4 cm), II, or IIIA NSCLC. In combination w/ platinum & fluorouracil (FU) for the 1st-line treatment of patients w/ metastatic or w/ unresectable, recurrent head & neck squamous cell carcinoma (HNSCC). Single agent for the 1st-line treatment of patients w/ metastatic or w/ unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by a validated test. Monotherapy for the treatment of adult & ped patients ≥3 yr w/ relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT is not a treatment option. In combination w/ enfortumab vedotin for the 1st-line treatment of unresectable or metastatic urothelial carcinoma in adults. Treatment of patients w/ locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy & whose tumors express PD-L1 (CPS ≥10) as determined by a validated test, or in patients who are 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. 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/ fluoropyrimidine, oxaliplatin, & irinotecan. 1st-line treatment of patients w/ unresectable or metastatic MSI-H or dMMR CRC. In combination w/ trastuzumab, fluoropyrimidine- & platinum-containing chemotherapy for the 1st-line treatment of adults w/ locally advanced unresectable or metastatic HER2 +ve gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by a validated test. In combination w/ fluoropyrimidine- & platinum-containing chemotherapy for the 1st-line treatment of adults w/ locally advanced unresectable or metastatic HER2 -ve gastric or GEJ adenocarcinoma 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 GEJ adenocarcinoma (tumour centre 1-5 cm above the GEJ) 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. In combination w/ chemoradiotherapy (external beam RT followed by brachytherapy) for the treatment of FIGO 2014 stage III-IVA locally advanced cervical cancer in adults who have not received prior definitive therapy. 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. Treatment of patients w/ hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen. In combination w/ gemcitabine & cisplatin for the treatment of patients w/ locally advanced unresectable or metastatic biliary tract cancer (BTC). 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/ carboplatin & paclitaxel for the 1st-line treatment of primary advanced or recurrent endometrial carcinoma in adults who are candidates for systemic therapy. In combination w/ lenvatinib for the treatment of adult patients w/ advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not MSI-H as determined by a validated test, who have disease progression following prior systemic therapy in any setting & are not candidates for curative surgery or radiation. 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. 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/ CPS ≥10 & who have not received prior chemotherapy for metastatic disease.

Administer as 30-min IV infusion. Adult Monotherapy for unresectable or metastatic melanoma 200 mg every 3 wk or 400 mg every 6 wk, until disease progression or unacceptable toxicity. Monotherapy for adjuvant treatment of melanoma, NSCLC, or RCC 200 mg 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, HCC, or TMB-H cancer 200 mg 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 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 resectable NSCLC 200 mg 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 12 wk or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment w/ Keytruda as a single agent after surgery for 39 wk or until disease recurrence or unacceptable toxicity. Combination therapy for NSCLC, HNSCC, HER2 -ve gastric cancer, esophageal cancer, or BTC 200 mg 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 locally advanced or metastatic urothelial cancer 200 mg every 3 wk or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or up to 24 mth. Administer after enfortumab vedotin when given on the same day. Combination therapy for HER2 +ve gastric cancer 200 mg every 3 wk or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or up to 24 mth. Administer prior to trastuzumab & chemotherapy when given on the same day. Combination therapy for cervical cancer 200 mg every 3 wk or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or for Keytruda, up to 24 mth. Administer prior to chemoradiotherapy or prior to chemotherapy w/ or w/o bevacizumab when given on the same day. Combination therapy for RCC 200 mg every 3 wk or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or for Keytruda, up to 24 mth. Administer in combination w/ oral axitinib 5 mg bd or oral lenvatinib 20 mg once daily. Combination therapy for endometrial carcinoma 200 mg every 3 wk or 400 mg every 6 wk, until disease progression, unacceptable toxicity, or for Keytruda, up to 24 mth. Administer prior to carboplatin & paclitaxel when given on the same day or in combination w/ oral lenvatinib 20 mg once daily. Combination therapy for high-risk early-stage TNBC 200 mg 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 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 every 3 wk, up to a max of 200 mg, until disease progression, unacceptable toxicity, or up to 24 mth. Monotherapy for adjuvant treatment of melanoma 2 mg/kg every 3 wk, up to a max of 200 mg, until disease recurrence, unacceptable toxicity, or up to 12 mth.

Immune-mediated pneumonitis: W/hold for grade 2 pneumonitis. Permanently discontinue for grade 3 or 4 pneumonitis. Immune-mediated colitis: W/hold for grade 2 or 3 colitis. Permanently discontinue for grade 4 colitis. Immune-mediated hepatitis w/o tumor involvement of the liver: W/hold if AST or ALT increases >3 to 8x ULN or total bilirubin increases >1.5 to 3x ULN. Permanently discontinue if AST or ALT increases >8x ULN or total bilirubin increases >3x ULN. In combination w/ axitinib: W/hold both Keytruda & axitinib if ALT or AST increases ≥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 increases >3x ULN w/ concurrent total bilirubin ≥2x ULN or ALT or AST ≥10x ULN. Immune-mediated hepatitis w/ tumor involvement of the liver: W/hold if baseline AST or ALT >1 to 3x ULN & increases >5 to 10x ULN or baseline AST or ALT >3 to 5x ULN & increases >8 to 10x ULN. Permanently discontinue if AST or ALT increases >10x ULN or total bilirubin increases >3x ULN. Immune-mediated endocrinopathies: W/hold for grade 3 or 4 endocrinopathies until clinically stable or permanently discontinue depending on severity. Immune-mediated nephritis w/ renal dysfunction: W/hold for grade 2 or 3 increased blood creatinine. Permanently discontinue for grade 4 increased blood creatinine. Immune-mediated exfoliative dermatologic conditions: W/hold for suspected SJS, TEN, or DRESS. Permanently discontinue for confirmed SJS, TEN, or DRESS. Immune-mediated myocarditis: Permanently discontinue for grade 2, 3, or 4 myocarditis. Immune-mediated neurological toxicities: W/hold for grade 2 neurological toxicities. Permanently discontinue for grade 3 or 4 neurological toxicities. Immune-mediated hematologic toxicity in patients w/ cHL: W/hold 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. Can cause 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. Women should not breastfeed during treatment & for 4 mth after the last dose. Safety & effectiveness in ped patients have not been established in approved indications other than melanoma, cHL & TMB-H cancer. Safety & effectiveness in ped patients w/ TMB-H CNS cancers have not been established.

As single agent: Fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, hypothyroidism. In combination w/ chemotherapy or chemoradiotherapy: 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, palmar-plantar erythrodysesthesia, UTI, hypothyroidism. 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. In combination w/ enfortumab vedotin: Rash, peripheral neuropathy, fatigue, pruritus, diarrhea, alopecia, wt loss, decreased appetite, dry eye, nausea, constipation, dysgeusia, UTI.

Targeted Cancer Therapy / Cancer Immunotherapy

L01FF02 - pembrolizumab ; Belongs to the class of PD-1/PD-L1 (Programmed cell death protein 1/death ligand 1) inhibitors. Used in the treatment of cancer.

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