Keytruda (pembrolizumab)

They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAFV600E mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms...For example, BRAFV600E and IDH1/2 mutations; ALK, FGFR, and NTRK fusions; PD-L1 amplification; and CD70 antigens are druggable in both solid and blood malignancies by gene-/immune-targeted therapies/chimeric antigen receptor T cells. Future biomarker-based tissue-agnostic basket studies/approvals should bridge the great divide and include both solid and hematologic cancers.

P2, N=14, Active, not recruiting, Georgetown University | Trial completion date: Dec 2023 --> Dec 2024

In each case, checkpoint blockade led to durable radiographic responses. We therefore propose that it is reasonable to assess combined positive score and tumor mutational burden in refractory or recurrent pancreatic cancers when initiation of ICB is being considered.

Today, novel agents called antibody drug conjugates (ADCs), including enfortumab vedotin (EV) and sacituzumab govitecan (SG), have been approved for la/mUC offering patients treatment options following or instead of traditional chemotherapy...In 2023, EV in combination with pembrolizumab almost doubled progression-free and overall survival versus platinum-based chemotherapy, which led to accelerated FDA approval as first-line treatment for all patients with la/mUC...Finally, a recent cancer agnostic accelerated approval for trastuzumab deruxtecan (T-DXd) in HER2-positive (IHC3+) solid tumors provides another active ADC option for biomarker-selected patients with treatment refractory la/mUC. Several new ADCs are being investigated in urothelial cancer (UC) clinical trials. This review summarizes the clinical studies and real-world data regarding the use of ADCs in UC.

Pembrolizumab alone or combined with chemotherapy indicates an effective and safe treatment for metastatic cancer. Pembrolizumab alone or combined with chemotherapy provides a better survival advantage under first-line treatment or programmed cell death ligand 1 combined positive scores of at least 10 or programmed cell death ligand 1 tumor proportion scores of at least 50%. However, we found that the specific efficacy of pembrolizumab in unused tumor types could not be effectively evaluated.

This review analyzes the current landscape of existing randomized clinical trials, highlighting the efficacy of immune checkpoint inhibitors (ICIs) like pembrolizumab, avelumab, and dostarlimab. These findings underscore the importance of tailoring treatments based on the molecular characteristics of each tumor and paving the way for future advancements in the field of gynecologic oncology. Despite promising results, this article acknowledges the necessity of further research to refine patient selection criteria and explore combination strategies that can overcome resistance mechanisms.

By blocking this interaction, checkpoint inhibitors such as nivolumab and pembrolizumab have demonstrated high response rates in patients with cHL, particularly in those who have not responded to conventional therapies. By understanding how TNF signaling interacts with immune checkpoints, researchers can design more effective treatment regimens that simultaneously target multiple pathways. Combining TNF inhibitors with checkpoint blockade therapies may enhance the overall anti-tumor response by addressing both direct tumor signaling and the immune evasion mechanisms employed by tumor cells.

This subgroup of IO-responsive NS-pts may have better prognosis. Our findings suggest that DDR-based mutational profiling may help identify NS-pts who could benefit from IO therapy.

Key to immunotherapy efficacy in EC is the tumor's mismatch repair status, with MMR-deficient tumors demonstrating a higher tumor mutational burden and increased PD-L1 expression, making them more susceptible to immune checkpoint inhibitors (ICIs) such as pembrolizumab, durvalumab, and dostarlimab. To overcome resistance in cold tumors, novel therapies, including Chimeric Antigen Receptor (CAR) T cells and tumor-infiltrating lymphocytes are being explored, offering targeted immune-based strategies to enhance treatment efficacy. This review discusses the current understanding of immunotherapy in EC, emphasizing the prognostic and therapeutic implications of MMR status, TME composition, and emerging cell-based therapies.

Considering the frailty associated with cachexia, ICI monotherapy may be preferred to ICI/chemotherapy for these patients. New interventions that can better address the negative prognostic impact of cachexia in patients treated using ICIs with or without chemotherapy remain warranted.

Higher TMB was associated with objective response to ICI, however, TMB was an imperfect biomarker for PFS and OS in our study.

P=N/A, N=80, Recruiting, Hunan Cancer Hospital

P1, N=41, Not yet recruiting, VLP Therapeutics

P1/2, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Sep 2023 --> May 2025

P1/2, N=97, Active, not recruiting, NextCure, Inc. | Recruiting --> Active, not recruiting | N=209 --> 97

P2, N=166, Terminated, SOTIO Biotech AG | Active, not recruiting --> Terminated; Due to lack of expected efficacy shown at the time of the interim analysis

P2, N=40, Recruiting, ImmunityBio, Inc. | Active, not recruiting --> Recruiting | N=147 --> 40

P1, N=18, Recruiting, University of Southern California | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026

P1, N=40, Recruiting, Microbiotica Ltd | Not yet recruiting --> Recruiting

This study suggests that immunotherapy is less beneficial in SCC-MU. More work is needed to verify our findings and explore other treatment options.

Some elderly patients with NSCLC and high PD-L1 expression might benefit from COMB; however, MONO is considered the preferred treatment. MONO may not be an effective or feasible treatment for patients with PS 2-3, even with high PD-L1 expression.

Improvements in ORR and PFS for L+P versus sunitinib in aRCC were observed consistently across a range of biomarker subgroups defined using RCC driver mutations, PD-L1, gene expression signatures, and molecular subtypes.

P=N/A, N=40, Recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

P2, N=90, Not yet recruiting, Merck Sharp & Dohme LLC

P2, N=320, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Nov 2025 --> Jun 2027 | Trial primary completion date: Oct 2025 --> Jun 2026

P1/2, N=200, Recruiting, Linnaeus Therapeutics, Inc. | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Mar 2024 --> Dec 2026

P2, N=19, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P1, N=7, Active, not recruiting, National Cancer Institute (NCI) | N=37 --> 7 | Trial completion date: Nov 2024 --> Dec 2025

P2, N=19, Not yet recruiting, Roswell Park Cancer Institute | Trial completion date: Oct 2026 --> Feb 2027 | Trial primary completion date: Oct 2026 --> Feb 2027

P1/2, N=225, Recruiting, Tango Therapeutics, Inc. | N=159 --> 225

P1, N=230, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2025 --> Jun 2025 | Trial primary completion date: Feb 2025 --> Jun 2025

P3, N=726, Not yet recruiting, Daiichi Sankyo

P2, N=20, Not yet recruiting, Emory University

P2, N=40, Not yet recruiting, Virginia Commonwealth University

P2, N=13, Completed, Samsung Medical Center | Recruiting --> Completed | N=50 --> 13 | Trial completion date: Feb 2026 --> Dec 2024 | Trial primary completion date: Sep 2025 --> Jun 2024

P2, N=48, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2025 --> Dec 2025 | Trial primary completion date: Jul 2025 --> Dec 2025

P1/2, N=1, Terminated, Celularity Incorporated | N=52 --> 1 | Trial completion date: Feb 2025 --> Feb 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2023 --> Feb 2024; for business reasons

While the MMRd/MSI carcinoma was recognized early and showed complete pathologic response after pembrolizumab treatment, the MMRp/MSS adenocarcinoma was underrecognized and poorly responsive to treatment. A second patient, with a pathogenic PMS2 variant, also developed a MMRp CRC. These cases highlight the complex biological pathways in CRC development and the impact of molecular classification on treatment.

P1/2, N=120, Active, not recruiting, MedPacto, Inc. | Trial completion date: Aug 2024 --> Jan 2025

P2, N=25, Recruiting, Mayo Clinic | Not yet recruiting --> Recruiting

P2/3, N=542, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: May 2027 --> Dec 2025

P3, N=1397, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2028 --> Nov 2034