Keytruda (pembrolizumab)

P2, N=25, Not yet recruiting, Mayo Clinic

P1/2, N=1, Terminated, iOx Therapeutics | Trial completion date: Dec 2026 --> Apr 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2026 --> Apr 2024; Prioritization of other pipeline assets. No safety or efficacy issues were observed.

P1, N=34, Completed, MiNK Therapeutics | Recruiting --> Completed

Starting in 2017, four programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors-avelumab, pembrolizumab, nivolumab (utilized in both neoadjuvant and adjuvant settings), and retifanlimab-have demonstrated efficacy in treating patients with disseminated MCC on the basis of prospective clinical trials. Nevertheless, while randomized studies directly comparing immune checkpoint inhibitors and chemotherapy in MCC are lacking, immunotherapy shows response rates comparable to those previously reported with chemotherapy but with more enduring responses. Notably, adjuvant nivolumab has proven superiority to the standard-of-care therapy (observation) in the adjuvant setting.

In conclusion, sPD-L1 measured in baseline serum samples may be associated with OS in NSCLC patients receiving anti-PD1/anti-PD-L1 treatment. Importantly, the results signify that further research is warranted to explore the clinical utility of sPD-L1 in patients treated with anti-PD-L1.

P2, N=55, Active, not recruiting, Calliditas Therapeutics Suisse SA | Trial completion date: Jun 2024 --> Sep 2024

P4, N=50, Recruiting, Samsung Medical Center | Trial completion date: Aug 2023 --> Aug 2024

P1/2, N=70, Recruiting, Vyriad, Inc. | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=50, Active, not recruiting, Eikon Therapeutics | Trial primary completion date: Mar 2024 --> Aug 2024 | Trial completion date: Mar 2024 --> Aug 2024

P3, N=448, Recruiting, Mural Oncology, Inc | Active, not recruiting --> Recruiting | Trial completion date: Dec 2026 --> May 2027 | Trial primary completion date: Dec 2025 --> May 2026

P2, N=80, Active, not recruiting, Peking Union Medical College Hospital | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2027

P2, N=138, Active, not recruiting, University of Texas Southwestern Medical Center | Recruiting --> Active, not recruiting

In the whole-population network meta-analysis, the newly first-line tremelimumab plus durvalumab (Tre + Du) was found to be comparable with atezolizumab plus bevacizumab (Atezo + Beva) in providing the best overall survival (OS) benefit [hazard ratio (HR) 1.35, 95% confidence interval (CI): 0.93-1.92]. Concerning OS benefits, sintilimab plus bevacizumab biosimilar (Sint + Beva), camrelizumab plus rivoceranib (Camre + Rivo), and lenvatinib plus pembrolizumab (Lenva + Pemb) appear to exhibit similar effects to Tre + Du and Atezo + Beva...With lower incidence rates of treatment-related adverse events and non-inferior efficacy compared to sorafenib, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI-combined therapies. PROSPERO, CRD42022288172.

P1, N=3, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

P2, N=71, Recruiting, Memorial Sloan Kettering Cancer Center

P1, N=282, Recruiting, Amgen | Not yet recruiting --> Recruiting

P1, N=12, Completed, University of Chicago | Recruiting --> Completed | N=26 --> 12

P1/2, N=113, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

P2, N=28, Not yet recruiting, Masonic Cancer Center, University of Minnesota

On the other hand, there are some approved drugs, such as pembrolizumab for TMB-H or entrectinib or larotrectinib for NTRK fusion gene, for which there is no stand-alone companion diagnostics and the eligibility for these drugs cannot be judged without the results of CGP test. This paper discusses the current status and issues of companion diagnostics in cancer genomic medicine.

Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases)...Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.

P3; With ∼5 years of follow-up, pembrolizumab plus chemotherapy provided clinically meaningful and durable improvements in survival outcomes versus chemotherapy alone in patients with previously untreated metastatic NSCLC with PD-L1 TPS <1%. These results continue to support pembrolizumab plus chemotherapy as a standard of care in this patient population.

P1, N=18, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P1, N=18, Completed, Lyvgen Biopharma Holdings Limited | Terminated --> Completed

P1, N=43, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting | N=21 --> 43

P3, N=1250, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting

P2, N=77, Active, not recruiting, Seoul National University Hospital | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=10, Terminated, Incyte Corporation | Active, not recruiting --> Terminated; A business decision due to availability of commercial drug and other options for accessing study drug treatment.

Moreover, TXNRD1 inhibition through auranofin cotreatment synergized with anti-PD-1 therapy to potentiate immunotherapy-mediated ferroptosis by mediating CD8+ T-cell infiltration and downregulating PD-L1 expression. Our findings indicate that targeting TXNRD1 is a promising therapeutic strategy for improving immunotherapy outcomes in patients with HNSCC.

P1/2, N=120, Active, not recruiting, MedPacto, Inc. | Phase classification: P1b/2a --> P1/2 | N=67 --> 120 | Trial completion date: Aug 2023 --> Aug 2024 | Trial primary completion date: Jun 2021 --> May 2024

P2, N=60, Recruiting, University of Wisconsin, Madison | Trial completion date: Dec 2025 --> Oct 2026 | Trial primary completion date: Mar 2024 --> Jan 2025

P2, N=14, Terminated, Hoosier Cancer Research Network | Active, not recruiting --> Terminated; Study failed to meet its interim analysis endpoint

P2/3, N=1012, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P1/2, N=47, Terminated, Sumitomo Pharma America, Inc. | Phase classification: P1b/2 --> P1/2 | Completed --> Terminated; Sponsor's decision to terminate development of the program.

P1, N=492, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2024 --> Aug 2024 | Trial primary completion date: Oct 2024 --> Aug 2024

P1, N=175, Active, not recruiting, Tempest Therapeutics | Recruiting --> Active, not recruiting | Phase classification: P1a/1b --> P1 | Trial primary completion date: Apr 2024 --> Sep 2024

P1/2, N=31, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: May 2024 --> Oct 2023

P1/2, N=400, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P2, N=20, Recruiting, Saint Petersburg State University, Russia

P2, N=19, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | N=30 --> 19 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

While in cohort A pembrolizumab lacked activity, cohort B and cohort C met the study's primary endpoint. Further research is warranted to refine selection of patients with tumors harboring lower TMLs and may benefit from a focus on innate immunity.

Eight drugs have been approved by the FDA for HNC, including both generic and commercial forms: bleomycin sulfate, cetuximab (Erbitux), docetaxel (Taxotere), hydroxyurea (Hydrea), pembrolizumab (Keytruda), loqtorzi (Toripalimab-tpzi), methotrexate sodium (Trexall), and nivolumab (Opdivo). The most common drugs to treat HPV-associated OPC under these clinical trials and implemented as well for HPV-negative HNC include cisplatin, nivolumab, cetuximab, paclitaxel, pembrolizumab, 5-fluorouracil, and docetaxel...In this context, we identified most mutated genes found in HPV-associated OPC that can represent potential targets for drug development. These include TP53, PIK3CA, PTEN, NOTCH1, RB1, FAT1, FBXW7, HRAS, KRAS, and CDKN2A.