Merck’s (MRK) anti-PD-1 drug Keytruda® (pembrolizumab) is approved for many, many cancers. Yet, it is fair to say that this checkpoint inhibitor drug will not be effective in all cancers. This is especially true now that yesterday, the U.S. Food and Drug Administration (FDA) has placed a clinical hold on KEYNOTE-183, KEYNOTE-185 and KEYNOTE-023, three combination studies of Keytruda® with Celgene’s products Pomalyst Pomalidomide and Revlimid lenalidomide intended for the treatment of multiple myeloma.
This decision follows a review of data by the Data Monitoring Committee in which more deaths were observed in the Keytruda arms of KEYNOTE-183 and KEYNOTE-185 and which led to the pause in new patient enrollment, as announced on June 12, 2017. The FDA has determined that the data available at the present time indicate that the risks of Keytruda plus Pomalidomide or lenalidomide outweigh any potential benefit for patients with multiple myeloma. All patients enrolled in KEYNOTE-183 and KEYNOTE-185 and those in Keytruda/lenalidomide and dexamethasone cohort in KEYNOTE-023 will discontinue investigational treatment with Keytruda.
This clinical hold does not apply to other studies with Keytruda.
Studies placed on full clinical hold:
KEYNOTE-183: “A Phase 3 study of Pomalidomide and low-dose Dexamethasone with or without Pembrolizumab (MK3475) in refractory or relapsed and refractory Multiple Myeloma KEYNOTE-183”
KEYNOTE-185: “A Phase 3 study of Lenalidomide and low-dose Dexamethasone with or without Pembrolizumab (MK3475) in newly diagnosed and treatment naïve Multiple Myeloma (KEYNOTE-185).”
A study placed on partial clinical hold:
KEYNOTE-023 Cohort 1: “A Phase I Multi-Cohort Trial of Pembrolizumab (MK-3475) in Combination with Backbone Treatments for Subjects with Multiple Myeloma (KEYNOTE 023).” Cohort 1 of KEYNOTE-023 evaluated Keytruda in combination with Pomalyst and dexamethasone in patients who received prior anti-multiple myeloma treatment with an immunomodulatory (IMiD) treatment (lenalidomide, pomalidomide or thalidomide).
Valuable Information
Keytruda ® (pembrolizumab) Injection Indications and Dosing
Melanoma
Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.
Lung Cancer
Keytruda, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
Keytruda, as a single agent, is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda.
Keytruda, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In metastatic NSCLC, keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
When administering Keytruda in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin.
Head and Neck Cancer
Keytruda in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Classical Hodgkin Lymphoma
Keytruda is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In adults with cHL, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with cHL, Keytruda is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Urothelial Carcinoma
Keytruda (pembrolizumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Keytruda is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Microsatellite Instability-High (MSI-H) Cancer
Keytruda is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
– solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
– colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of Keytruda in pediatric patients with MSI-H central nervous system cancers have not been established.
In adult patients with MSI-H cancer, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with MSI-H cancer, Keytruda is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Prohost Observations
Again we say that although Keytruda has been approved in all the above mentioned cancers, one must not expect this checkpoint inhibitor immunotherapy to demonstrate efficacy in all kinds of cancers. We still sincerely believe that immune checkpoint inhibitors represent a huge step forward towards saving lives of cancer patients whose malignancies have exhausted all existing treatments, leaving the victims with no hope for survival.
We believe that Keytruda’s combination failure in multiple myeloma should not be taken advantage of for the sake of spreading suspicion about the Keytruda’s efficacy. It is obvious that the number of cancers the FDA has already approved Keytruda to treat exceeds, by far, the FDA banning of the combination intended for multiple myeloma.
Merck’s Keytruda: Extremely Valuable, But Not for Multiple Myeloma
Merck’s (MRK) anti-PD-1 drug Keytruda® (pembrolizumab) is approved for many, many cancers. Yet, it is fair to say that this checkpoint inhibitor drug will not be effective in all cancers. This is especially true now that yesterday, the U.S. Food and Drug Administration (FDA) has placed a clinical hold on KEYNOTE-183, KEYNOTE-185 and KEYNOTE-023, three combination studies of Keytruda® with Celgene’s products Pomalyst Pomalidomide and Revlimid lenalidomide intended for the treatment of multiple myeloma.
This decision follows a review of data by the Data Monitoring Committee in which more deaths were observed in the Keytruda arms of KEYNOTE-183 and KEYNOTE-185 and which led to the pause in new patient enrollment, as announced on June 12, 2017. The FDA has determined that the data available at the present time indicate that the risks of Keytruda plus Pomalidomide or lenalidomide outweigh any potential benefit for patients with multiple myeloma. All patients enrolled in KEYNOTE-183 and KEYNOTE-185 and those in Keytruda/lenalidomide and dexamethasone cohort in KEYNOTE-023 will discontinue investigational treatment with Keytruda.
This clinical hold does not apply to other studies with Keytruda.
Studies placed on full clinical hold:
KEYNOTE-183: “A Phase 3 study of Pomalidomide and low-dose Dexamethasone with or without Pembrolizumab (MK3475) in refractory or relapsed and refractory Multiple Myeloma KEYNOTE-183”
KEYNOTE-185: “A Phase 3 study of Lenalidomide and low-dose Dexamethasone with or without Pembrolizumab (MK3475) in newly diagnosed and treatment naïve Multiple Myeloma (KEYNOTE-185).”
A study placed on partial clinical hold:
KEYNOTE-023 Cohort 1: “A Phase I Multi-Cohort Trial of Pembrolizumab (MK-3475) in Combination with Backbone Treatments for Subjects with Multiple Myeloma (KEYNOTE 023).” Cohort 1 of KEYNOTE-023 evaluated Keytruda in combination with Pomalyst and dexamethasone in patients who received prior anti-multiple myeloma treatment with an immunomodulatory (IMiD) treatment (lenalidomide, pomalidomide or thalidomide).
Valuable Information
Keytruda ® (pembrolizumab) Injection Indications and Dosing
Melanoma
Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.
Lung Cancer
Keytruda, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
Keytruda, as a single agent, is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda.
Keytruda, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In metastatic NSCLC, keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
When administering Keytruda in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin.
Head and Neck Cancer
Keytruda in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Classical Hodgkin Lymphoma
Keytruda is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In adults with cHL, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with cHL, Keytruda is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Urothelial Carcinoma
Keytruda (pembrolizumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Keytruda is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Microsatellite Instability-High (MSI-H) Cancer
Keytruda is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
– solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
– colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of Keytruda in pediatric patients with MSI-H central nervous system cancers have not been established.
In adult patients with MSI-H cancer, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with MSI-H cancer, Keytruda is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Prohost Observations
Again we say that although Keytruda has been approved in all the above mentioned cancers, one must not expect this checkpoint inhibitor immunotherapy to demonstrate efficacy in all kinds of cancers. We still sincerely believe that immune checkpoint inhibitors represent a huge step forward towards saving lives of cancer patients whose malignancies have exhausted all existing treatments, leaving the victims with no hope for survival.
We believe that Keytruda’s combination failure in multiple myeloma should not be taken advantage of for the sake of spreading suspicion about the Keytruda’s efficacy. It is obvious that the number of cancers the FDA has already approved Keytruda to treat exceeds, by far, the FDA banning of the combination intended for multiple myeloma.
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