Keytruda (pembrolizumab)

Combined paclitaxel/CKM regimen was safe, with desirable TME changes and preliminary indications of promising pCR+ypTmic of 66%, comparable to the combination of NAC with pembrolizumab.

Fourteen different articles showed that the use of cytokines and cancer vaccines revealed new possibilities to treat breast cancer with antibodies against PD-1/PD-L1 (pembrolizumab), PI3K/Akt/mTOR (alpelisib and everolimus), CAR T-cell (chimeric antigen receptor), PARP (poly ADP-ribose polymerase), and CTLA4 (cytotoxic T-lymphocyte-associated protein 4), and with representative relevance of changing in tumor microenvironment. Estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) targets show also a high effectivity. In recent years, the release of new strategies has become promising, for changing the microenvironment and de-escalation of therapy based on tumor biology, novel biomarkers, and tumor spread.

Notably, there was no difference in the incidence of immune-related AEs. In patients with mUC who received pembrolizumab, CRP flare-responders showed favorable oncological outcomes; therefore, BL CRP levels could predict oncological outcomes in CRP flare-responders.

Dose-dense chemotherapy regimens and the addition of carboplatin have been associated with an improvement in these response rates. Furthermore, immunotherapy, particularly pembrolizumab, has shown significant benefits in terms of recurrence-free survival...In conclusion, despite recent progress, TNBC remains a major clinical challenge. A better understanding of its biology and a personalized therapeutic approach are essential to improve clinical outcomes for patients with this aggressive form of breast cancer.

Despite the rarity of NTRK fusions in pancreatic cancer, larotrectinib and entrectinib have exhibited effectiveness in NTRK fusion-positive pancreatic cancers. Additionally, repotrectinib, a next-generation NTRK inhibitor, has shown promising activity in NTRK positive pancreatic cancer patients who have developed acquired resistance to previous NTRK inhibitors. Immune checkpoint inhibitors, such as pembrolizumab and dostarlimab, have proven to be effective in dMMR/MSI-H pancreatic cancers...It is crucial to continue implementing comprehensive screening strategies that encompass the ability to detect all these tumor-agnostic biomarkers. This will be essential in identifying pancreatic cancer patients who may benefit from these therapies.

These monoclonal antibodies target immune checkpoints, including cytotoxic T-lymphocyte-associated protein 4 (ipilimumab and tremelimumab), programmed death 1 (nivolumab, pembrolizumab, cemiplimab, and dostarlimab), programmed death ligand 1 (atezolizumab, avelumab, and durvalumab), and lymphocyte activation gene 3 (relatlimab), and effectively augment the immune response against tumor cells. Despite clinical improvements with immunomodulatory therapy, with corticosteroids the mainstay of treatment, mortality remains high, particularly in those with associated myocarditis or respiratory failure requiring intubation, where mortality occurs in up to 50%. ICI withdrawal can lead to cancer progression and death, highlighting a need for improved approaches to ICI rechallenge, performed in limited patients with variable success to date.

Our real-world data indicate that combined CTLA-4 and PD-1 blockade is most beneficial for patients with multi-organ metastasis, while those with oligo-organ metastasis fare better with PD-1 monotherapy. The underlying reasons for these observations-whether they are due to differences in the characteristics of multi- and oligo-metastatic melanomas or the risk-benefit profile of the therapies-remain to be elucidated. These findings underscore the need for a nuanced approach to treatment regimens for stage IV melanoma patients.

The results of this study offer insights into the real-world use of pembrolizumab as an adjuvant therapy for melanoma in Europe.

P2, N=33, Recruiting, North Eastern German Society of Gynaecological Oncology | Trial primary completion date: Nov 2024 --> Apr 2025

P2, N=43, Active, not recruiting, National Cancer Center Hospital East | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2025 --> Aug 2026

P1/2, N=484, Recruiting, Revolution Medicines, Inc. | N=352 --> 484

P2, N=20, Recruiting, University of Florida | Not yet recruiting --> Recruiting

P=N/A, N=160, Recruiting, University Hospital, Montpellier | Not yet recruiting --> Recruiting

P2, N=28, Completed, Yonsei University | N=18 --> 28

P1/2, N=316, Recruiting, Simcha IL-18, Inc. | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Jun 2025

P1, N=78, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=37, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jul 2031 --> Jan 2032 | Initiation date: Nov 2024 --> May 2025 | Trial primary completion date: Jul 2030 --> Jan 2031

P1, N=110, Completed, Vincerx Pharma, Inc. | Active, not recruiting --> Completed

P1, N=353, Completed, Eli Lilly and Company | Active, not recruiting --> Completed

P2, N=603, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P2, N=20, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

While combination therapies, including immunotherapies, have shown positive outcomes, immune checkpoint inhibitors like nivolumab and pembrolizumab have demonstrated encouraging antitumor activity. Additionally, targeting the c-MET pathway has proven effective in certain papillary RCC. Further research is warranted to establish optimal treatment strategies and improve outcomes for patients with non-clear cell RCC. Systemic therapy for non-clear cell RCC is complex and evolving. Further research is needed to delineate optimal treatment strategies for different histological subtypes and improve patient outcomes.

Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.

P1/2, N=12, Terminated, Atara Biotherapeutics | Phase classification: P1b/2 --> P1/2

P1/2, N=140, Recruiting, Krystal Biotech, Inc. | Phase classification: P1 --> P1/2 | N=80 --> 140

P3, N=510, Recruiting, Akeso | Not yet recruiting --> Recruiting

P2, N=29, Recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2027 --> Nov 2028 | Trial primary completion date: Nov 2024 --> Nov 2025

P1/2, N=137, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

P2, N=692, Recruiting, Seagen Inc. | Trial primary completion date: Apr 2025 --> Feb 2026

P3, N=340, Active, not recruiting, Merck Sharp & Dohme LLC | N=800 --> 340 | Trial completion date: Jul 2028 --> Mar 2025 | Trial primary completion date: Jul 2028 --> Mar 2025

P1, N=572, Recruiting, Seagen Inc. | N=430 --> 572 | Trial completion date: Jan 2027 --> Nov 2027 | Trial primary completion date: Jun 2025 --> Nov 2027

P3, N=726, Not yet recruiting, mAbxience Research S.L.

P1/2, N=39, Active, not recruiting, Umar Farooq | Suspended --> Active, not recruiting

P2, N=35, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

P1, N=169, Completed, Astellas Pharma Global Development, Inc. | Phase classification: P1b --> P1

P2, N=348, Recruiting, West German Study Group | Not yet recruiting --> Recruiting

P2, N=169, Active, not recruiting, Arcus Biosciences, Inc. | Phase classification: P3 --> P2 | Trial primary completion date: Aug 2024 --> May 2027

P2, N=101, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P4, N=20, Recruiting, yangjianjun | Initiation date: Jan 2024 --> Sep 2024

P2, N=9, Active, not recruiting, Mayo Clinic | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P1/2, N=135, Recruiting, NuCana plc | N=94 --> 135 | Trial completion date: Jun 2024 --> Aug 2026 | Trial primary completion date: Jun 2024 --> Aug 2026

P2, N=340, Recruiting, GlaxoSmithKline | Trial completion date: Jan 2028 --> Oct 2028 | Trial primary completion date: Jan 2025 --> Oct 2025