P2, N=90, Not yet recruiting, Shanghai Henlius Biotech

In conclusion, this novel BsADC, through immune checkpoint inhibition and promotion of ICD, amplified durable tumor immune cytotoxicity, providing novel insights and potential avenues for future cancer treatments and overcoming resistance.

P1/2, N=360, Recruiting, DualityBio Inc. | Not yet recruiting --> Recruiting

P1, N=438, Recruiting, Seagen Inc. | Trial completion date: Dec 2026 --> Dec 2027

P1, N=438, Recruiting, Seagen Inc. | N=322 --> 438

P1/2, N=360, Not yet recruiting, DualityBio Inc.

P1, N=36, Recruiting, Shanghai Henlius Biotech | Not yet recruiting --> Recruiting

P1, N=36, Not yet recruiting, Shanghai Henlius Biotech

Conclusions HLX43 showed promising efficacy and tolerability in preclinical assessments. It may offer a novel treatment for PD-1/PD-L1 inhibitor R/R cancers like NSCLC, HNSCC, ESCC, MEL, and OVC.

Three ETBs (MT-0169, MT-5111, and MT-6402) are currently in clinical studies across different targets (CD38, HER2, PD-L1) and across hematologic malignancies, solid tumor, and immuno-oncology indications. ETBs can also deliver additional payloads to drive unique biology like the alteration of tumor immunophenotype. Here we describe three active clinical stage programs with encouraging safety and efficacy data that represent a transformation of the immunotoxin landscape into a more viable therapeutic approach to target validated as well as typically intractable clinical cancer targets.

Objective response rate will be analyzed by tumor type, dose levels, and schedules. Enrollment for Part A is ongoing at sites in North America and is planned in Europe.

Introduction MT-6402 is a de-immunized engineered toxin body (ETB) targeting PD-L1 for solid tumors that carries a Shiga-like Toxin-A (SLT-A) payload with the addition of cytomegalovirus (CMV) antigen seeding technology (AST)...In Part A, the starting dose will be 16 µg/kg based upon the highest non-severely toxic dose in non-human primates; in Part B, the starting dose will be the MTD determined in Part A. Treatment will continue until disease progression, unacceptable toxicity, death, withdrawal of consent, or another reason. Enrollment is estimated to begin at several US centers in the first half of 2021.

This is the largest Indian study demonstrating PD-L1 expression in NSCLC patients comparing with clinicopathologic and genomic parameters. PD-L1 expression was significantly associated with high-grade, solid, and acinar types of adenocarcinoma and advanced tumors. High PD-L1 expression was more prevalent in female patients, aged ≥60 years, smokers, and poorly differentiated and stage IV tumors (28.2 %). Exon 19 deletion was more in PD-L1 negative tumors whereas exon 21 substitution (L858R) was more in PD-L1 positive tumors. PD-L1 is a potential predictive marker stratifying patients who benefit from PD-1 pathway-targeted therapy.

The anti-tumor effect of PDI-1 in vivo was comparable to that of the anti-PD-L1 antibody atezolizumab. These results suggest that the small molecule inhibitors of PD-1/PD-L1 may be effective as an alternative or complementary immune checkpoint inhibitor to monoclonal antibodies.

This review summarizes the available data with immune-based therapeutic modalities such as monoclonal antibodies (naked and conjugated), T cell engagers, adoptive T-cell therapy, adoptive-NK therapy, checkpoint blockade via PD-1/PD-L1, CTLA4, TIM3 and macrophage checkpoint blockade via the CD47/SIRPa axis, and leukemia vaccines. Combining clinical results with biological immunological findings, possibly coupled with the discovery of biomarkers predictive for response, will hopefully allow us to determine the best approaches to immunotherapy in AML.

Among these are the type of cytological samples, pre-analytical issues, cyto-histological correlation, and inter-observer agreement. This review briefly summarizes the knowledge of the role of cytopathology in the analysis of PD-L1 by immunocytochemistry (ICC) and future directions of cytopathology in the immunotherapy setting.

Immune checkpoint inhibitors, including anti-PD-1 (nivolumab and pembrolizumab), anti-PD-L1 (Atezolizumab, avelumab, and duravulumab), and anti-CTLA-4 (ipilimumab, tremelimumab), are currently FDA-approved treatment options for a broad range of cancer types. Therefore, most antibodies against these immune checkpoints are undertaking clinical trials for cancer immunotherapy of advanced solid tumors and hematologic malignancies. In this review, we will summarize recent findings of immune checkpoint and the role of monoclonal antibodies in cancer immunotherapy targeting these receptors.

In this small study, there was a statistical increase in CD4, CD14, CD68, CD8A, B7-H3, PDL-1, CD19, FOXP3, CD44, and STAT3 protein expression in methylated versus unmethylated GBM tumour core; however, this requires larger cohort validation. Advanced multiplex immunooncological biomarker analysis may be useful in identifying biomarkers for novel immunotherapeutic agents in GBMs.

Summary: The combination of chemotherapy and immunotherapy is a potential therapeutic option for PD-L1-positive mTNBC, as the FDA recently approved atezolizumab (Tecentriq) and pembrolizumab (Keytruda) in combination with chemotherapy. Also, 2 targeted therapies-olaparib (Lynparza) and talazoparib (Talzenna)-are FDA approved for the management of mTNBC with germline BRCA mutations, and sacituzumab govitecan, an anti-Trop2 antibody-drug conjugate (ADC), was recently approved for previously treated mTNBC...Key Message: The successful clinical development of immunotherapies, PARP inhibitors, and ADCs for the management of mTNBC has improved the survival outcome of patients. Over the coming years, the therapeutic developments in precision medicine will likely change the mTNBC landscape, and might make the current definition of TNBC as breast cancer that is estrogen receptor negative, progesterone receptor negative, and HER2 negative obsolete.

Early results of the MonarchE trial investigating the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib to standard adjuvant endocrine therapy indicated a lower recurrence rate in the combination group in a high-risk population of patients with early stage hormone receptor (HR)-positive/HER2-negative BC. In contrast, the PALLAS study evaluating adjuvant palbociclib could not confirm these results...Final overall survival (OS) analysis of IMpassion130 confirmed the clinically relevant OS improvement observed with the addition of atezolizumab to first-line nab-paclitaxel in metastatic PD-L1 positive TNBC...Antibody-drug conjugates (ADCs) have been successfully established in HER2-positive breast cancer; in TNBC, the phase III ASCENT trial compared the ADC sacituzumab govitecan with chemotherapy by physician's choice in pretreated metastatic patients. A significant improvement in terms of progression-free survival and OS was observed rendering this drug a potential novel standard in this patient population.

These include bispecific and dual antigen receptor-targeting antibodies (targeted to CD33, CD123, CLL-1, and others), chimeric antigen receptor (CAR) T-cell therapies, and T-cell immune checkpoint inhibitors (including those targeting PD-1, PD-L1, CTLA-4, and newer targets such as TIM3 and STING). The current and future directions of these T-cell-based immunotherapies in the treatment landscape of AML are discussed in this review.

These results could be important to consider when designing future clinical trials of ICI treatment in pediatric patients with relapsed or refractory solid tumors.

Moreover, combination of LAG-3 with the immunomodulatory drug (IMiD) lenalidomide significantly increased IL-2 production by T cells and antibody-dependent cytotoxicity (ADCC) mediated by NK cells. Altogether, these data provide new insights into the potential anti-leukemic effects of relatlimab, currently in clinical trials in CLL, and provides the rationale to further investigate its combination with IMiDs for the management of hematological malignancies.

To the best of our knowledge, this is the first study that has assessed an anti-PD-1 antibody combined with a multi-target antiangiogenic TKI in the front-line setting for NSCLC patients. In view of its encouraging efficacy, durability, and safety profile, sintilimab plus anlotinib represents a novel chemotherapy-free regimen in this patient population.

There are promising ongoing monotherapy and combination therapy trials using different immune checkpoint inhibitors, poly adenosine diphosphate ribose polymerase inhibitors, tumor angiogenesis inhibitors (i.e., bevacizumab), antibody-drug conjugates, therapeutic vaccines, and tumor-infiltrating T lymphocytes (adoptive immunotherapy)...At this time, pembrolizumab is approved for the treatment of relapsed or metastatic programmed death ligand 1 (PD-L1) positive cervical cancer after frontline chemotherapy treatment. Multiple novel therapeutic modalities are emerging as safe and effective for the treatment of cervical cancer patients. Development and participation in investigative treatments can provide benefit and improve outcomes in cervical cancer.

The anti-PDL-1/ICOS antibody is new; however, only preclinical assays are shown using colon carcinoma model. So far, there are no reports of clinical trials to evaluate the safety, toxicity and efficacy, but it will be of great interest to analyze in the future if this antibody surpasses the action of the combinatorial therapy in cancer.

CD200/CD200R pathway is frequently expressed in lung cancer patients. Differential expression patterns of CD200 and CD200R with PD-L1 suggest a potential role for targeting this pathway alone in patients with NSCLC.

Bladder cancer is a complex disease, and its management is evolving. Advances in therapy, understanding of the disease, and advanced imaging have ushered in a period of rapid change in the care of bladder cancer patients.

Some targeted drugs were recently approved for these patients: two poly(ADP-ribose) polymerase inhibitors in patients with germline BRCA1/2 mutations (olaparib and talazoparib), immune checkpoint inhibitors in association with chemotherapy if programmed death-ligand 1 positive (atezolizumab plus nabpaclitaxel and pembrolizumab plus chemotherapy [nabpaclitaxel, paclitaxel, and carboplatin plus gemcitabine]), and an antibody-drug conjugate sacituzumab-govitecan in heavily pretreated patients (at least 2 previous lines for the metastatic setting). Soon, the treatment of metastatic TNBC could be based on personalized medicine using molecular testing for targeted drugs instead of only systemic chemotherapy. The authors present a review of emerging treatment options in metastatic TNBC, focusing on targeted drugs, including the recent data published in 2020.

The combination of pepinemab with avelumab was well tolerated in NSCLC and showed signs of antitumor activity in immunotherapy resistant and PD-L1 negative / low tumors.

The prevalence of oral mucositis is lower in new immunotherapy with monoclonal antibodies against oral cancer than drugs used so far (chemotherapy drugs [methotrexate, cisplatin] as well as cetuximab). However, more studies should be carried out to confirm these data.

Recent studies have demonstrated improved progression free survival with the combination of atezolizumab/pembrolizumab and chemotherapy in programmed death-ligand 1 positive metastatic TNBC. However, a recent trial in a similar population showed no benefit for atezoli-zumab and paclitaxel which led to a Food and Drug Administration alert. Two phase III trials (OLYMPIAD and BROCADE3) demonstrated a benefit in progression free survival (PFS) but not overall survival in patients with BRCA-associated metastatic TNBC treated with Olaparib or Talazoparib respectively...The BROCADE3 trial demonstrated that the combination of a platinum and veliparib increased PFS in first-line metastatic TNBC but at the cost of increased toxicity...This review focusses on recent and emerging therapeutic options in metastatic TNBC. We searched PubMed, clinicaltrials.gov and recent international meetings from American Society of Clinical Oncology, San Antonio Breast Cancer Conference and the European Society of Medical Oncology.

This is the first report of successful use of anlotinib combined with camrelizumab in the treatment of advanced primary ASPS. The treatment benefit provides preliminary evidence that targeted therapy, combined with immunotherapy, may be a safe and effective approach to treat primary pulmonary ASPS patients, thus warranting further investigation.

Preclinical data have guided the development of this clinical trial combining 1) BN-Brachyury (a poxvirus vaccine platform encoding the tumor associated antigen brachyury), 2) bintrafusp alfa (a bifunctional protein composed of the extracellular domain of the TGF-βRII receptor (TGFβ "trap") fused to a human IgG1 anti-PD-L1), 3), entinostat (a class I histone deacetylase inhibitor), and 4) T-DM1 (ado-trastuzumab emtansine, a standard of care antibody-drug conjugate targeting HER2). To our knowledge, the combination of a vaccine, an anti-PD-L1 antibody, entinostat, and T-DM1 has not been previously evaluated in the preclinical or clinical setting. This trial (NCT04296942) is open at the National Cancer Institute (Bethesda, MD).

The clinical data that supported the approval of EV are reviewed, and supporting safety and management considerations are provided based on the authors' experience. EV therapy can be optimized through patient and caregiver education, proactive patient monitoring, early identification of adverse events, and timely intervention to alleviate symptoms.

Chemo-immunotherapy combinations will become the new standard of care for some patients with metastatic oesophago-gastric cancers. Adjuvant nivolumab is a new option for oesophageal cancer patients with poor response after neoadjuvant chemoradiation.