Cervical cancer welcomes new targeted drugs; "unlimited cancer species" RET inhibitors have "strong efficacy"|Tumor News

*Only for medical professionals to read for reference, 1 minute a day, to give you professional "talking information" in the tumor circle! (If you need the original text of the document, you can add the editor WeChat yxj_oncology to obtain) Key points: NEJM: Oncolytic virus therapy G207 transforms immune "cold" tumors into "hot" tumors.
Lancet Oncol: PI3K inhibitor copanlisib combined with rituximab may be able to Brings new hope to relapsed indolent NHL Lancet Oncol: Cervical cancer welcomes a new targeted drug-tisotumab vedotin JTO: There is a potential causal relationship between marijuana use and the occurrence of lung squamous cell carcinoma 01 NEJM: Oncolytic virus therapy G207 will be immune A few days ago, The New England Journal of Medicine (NEJM) published an online phase I clinical trial showing that herpes simplex virus type 1 (HSV-1) G207 transforms immune “cold” tumors into “hot” tumors.
"Hot" tumors.

Article release screenshots Pediatric high-grade gliomas are immunologically "cold" tumors, with almost no tumor-infiltrating lymphocytes.

Preclinical studies have found that pediatric brain tumors are highly sensitive to the use of genetically engineered oncolytic virus therapy, and HSV-1 G207 lacks genes necessary for replication in normal brain tissue.

The phase I clinical trial adopted a 3+3 trial design with 4 dose groups, and included children and adolescents who were confirmed to be recurrent or progressive supratentorial brain tumors by biopsy.

The patient received 4 intratumoral catheters for stereotaxic, the next day, the catheter was infused with G207 (107 or 108 plaque-forming units), and dose groups 3 and 4 received radiation of the total tumor volume (5 Gy).

Analysis and evaluation of virus shedding in saliva, conjunctiva and blood, analysis and examination of tumor-infiltrating lymphocytes in tissue samples before and after treatment.

The results of the study showed that 12 high-grade glioma patients aged 7 to 18 received G207 treatment.
The investigator did not attribute dose-limiting toxic effects or serious adverse events to G207.
20 cases of grade 1 adverse events may be related to G207.
G207 is related.

Radiological, neuropathological, or clinical responses were found in 11 patients; median overall survival was 12.
2 months (95% CI 8.
0-16.
4); as of June 5, 2020, 18 months after receiving G207 treatment , 4 out of 11 patients were still alive; G207 significantly increased the number of tumor infiltrating lymphocytes.

02Lancet Oncol: PI3K inhibitor copanlisib combined with rituximab may bring new hope to relapsed indolent NHL.
Compared with rituximab, copanlisib plus rituximab can improve the progression-free survival (PFS) of patients with relapsed indolent non-Hodgkin lymphoma (NHL).

Copanlisib is the first PI3K inhibitor to be safely combined with rituximab, and the first drug to demonstrate the broad and excellent efficacy of combination therapy with rituximab in patients with relapsed indolent NHL.

Article release screenshots The CHRONOS-3 trial was randomized into groups (a total of 6 groups), using an interactive voice network response system to randomly assign patients (2:1) to copanlisib [60 mg, in cycles 1, 8 and 15 (28 days) ) In the cycle schedule of intravenous infusion for 1 hour] plus rituximab (on the first day 1, 8, 15 and 22 of the first cycle and the first day of the 3, 5, 7 and 9 cycles, intravenously every week Infusion of 375 mg/m2) or placebo plus rituximab group.

The results of the study showed that compared with the placebo plus rituximab group, the copanlisib plus rituximab group showed a statistically and clinically significant improvement in PFS: the median PFS in the trial group was 21.
5 months ( 95%CI 17.
8–33.
0), the control group was only 13.
8 months (95%CI 10.
2–17.
5; HR 0.
52, p<0.
0001).

The most common grade 3-4 adverse events were hyperglycemia (56% in the test group vs 8% in the control group) and hypertension (40% vs 9%).

In the copanlisib plus rituximab combination receiving placebo plus rituximab, 145 (47%) and 27 (18%) patients reported serious emergency treatment adverse events.

One case (<1%) drug-related death (pneumonia) occurred in the Copanlisib plus rituximab group.

03Lancet Oncol: Cervical cancer welcomes a new targeted drug-tisotumab vedotin.
Recently, The Lancet Oncology published a multi-center, open-label, single-arm, phase II study online, indicating that it has received treatment for recurrent or metastatic cervical cancer in the past Among female patients, tisotumab vedotin (TV for short) shows clinically significant and long-lasting anti-tumor activity, and has easy-to-handle and tolerable safety characteristics.

In view of the poor prognosis of this patient population, and the current treatments are less active in this case, if approved, TV will represent a new method for the treatment of recurrent or metastatic cervical cancer.

Screenshot of article release.
In this study, patients received intravenous TV at 20 mg/kg (up to 200 mg) every 3 weeks until the disease progressed (determined by the independent review committee) or unacceptable toxicity occurred.

The primary endpoint is the objective response rate (ORR).

The results of the study showed that the confirmed ORR was 24% (95%CI 16-33), of which 7% were complete remission (CR) and 17% were partial remission (PR).

The most common treatment-related adverse events included hair loss (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%) and dry eye (23%).

04JTO: There is a potential causal relationship between marijuana use and lung squamous cell carcinoma.
A few days ago, the Journal of Thoracic Oncology (JTO) published an online study showing that there is a relationship between the genetic responsibility of cannabis use and the risk of lung squamous cell carcinoma.
Potential causality.

Screenshot of the article released.
The study used Mendelian randomization (MR) to evaluate the impact of genetic factors on lifelong cannabis use and cannabis use disorders on lung function and lung cancer.

The study selected 4 types of single nucleotide polynucleotides related to lifetime use of cannabis from the genome-wide association study (GWAS) of 184765 European descent from the International Cannabis Federation, 23andme and UK Biobank.
Status (SNP) (P<5×10-8), use it as an instrumental variable.

From the GWAS meta-analysis of 17,068 European ancestry cases and 357,219 European ancestry control cases from the Psychiatric Genomics Consortium (PGC) Substance Use Disorders Working Group, iPSYCH and deCODE studies, 7 SNPs were selected (P<5×10- 8) As an instrumental variable for cannabis use disorder.

The lung function GWAS included 79,055 study participants from the SpiroMeta Alliance, and the lung cancer GWAS included 29,266 cases and 56,450 control cases from the International Lung Cancer Association (ILCCO).

The results of the study showed that the genetic responsibility of lifetime use of marijuana was associated with an increased risk of squamous cell carcinoma (OR=1.
22, 95% CI 1.
07-1.
39, P=0.
003).

The pleiotropic robust method and the positive and negative control analysis showed no bias in the main analysis.

The MR analysis results show that there is evidence that there is a potential causal relationship between the genetic responsibility of cannabis use and the risk of lung squamous cell carcinoma; triangulation and observational studies on MR to solve the source of orthogonal deviation are useful for confirming this A discovery is necessary.

References: [1]Friedman GK,Johnston JM,Bag AK,et al.
Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas.
N Engl J Med.
2021 Apr 10.
doi:10.
1056/NEJMoa2024947.
Epub ahead of print .
PMID:33838625.
[2]Matthew J Matasar,Marcelo Capra,MuhitÖzcan,et al.
Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma(CHRONOS-3):a double-blind,randomised,placebo -controlled,phase 3 trial.
published on April 10,2021.
doi:https://doi.
org/10.
1016/S1470-2045(21)00145-5[3]Robert L Coleman,Domenica Lorusso,Christine Gennigens,et al .
Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer(innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre,open-label,single-arm,phase 2 study.
published on April 09,2021.
doi:https://doi.
org/10/1016/S1470-2045(21)00056-5[4].
Sebastian-Edgar B,Hansjörg B, Michael N, et al.
Cannabis use, pulmonary function, and lung cancer susceptibility: A Mendelian randomization study.
J Thorac Oncol.
2021 Apr 11.
doi: https://doi.
org/10.
1016/j.
jtho.
2021.
03 .
025.