Pd1 antibody clinical trial

Inclusion Criteria: Participant is at least 18 years of age. Participant has proven recurrent or advanced solid tumor and has disease progression after treatment with available anti cancer therapies, or is intolerant to treatment that meets the following requirements for the part of the study they will participate in: a.

Part 1: Any histologically or cytologically proven recurrent advanced solid tumor b. Part 2A: : Any histologically or cytologically proven recurrent advanced solid tumor c.

Prior treatment with hormone therapies is acceptable and does not count towards the number of anti-cancer therapies noted in the criterion above for this cohort. All endometrial cancer histologies are allowed except endometrial sarcoma including carcinosarcoma. Participants must submit 2 scans demonstrating increase in tumor measurement that meet criteria for PD on or after the latest systemic anti-cancer therapy based on RECIST 1.

Presence of at least 1 measurable lesion on Baseline scan will be confirmed by central radiology review. After the central IHC test is completed, remaining tumor tissue may be tested for further exploratory biomarkers or may be sent to a central NGS laboratory for further testing. Cohort E - Participants with NSCLC who progressed after at least 1 prior platinum-based systemic chemotherapy regimen for recurrent or advanced disease. Prior treatment with hormone therapies alone given for recurrent or advanced disease is acceptable and does not count towards the number of anti-cancer therapies.

Progression following up to 3 prior lines of therapy is allowed. Ovarian cancer participants with platinum-resistant disease i. For participants with available local MMR IHC results for the respective cohort s , tumor samples have to be submitted to a central IHC laboratory and its quality has to be checked and cleared prior to C1D1. Participants who are considered for the study based on POLE mutation must have the local results available showing tumor mutation s in the exonuclease domain of the POLE gene amino acid residues to begin screening.

Participants must have the quality of submitted tumor samples checked and cleared by a central IHC laboratory prior to receiving study treatment. Cohort G: Participants must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer.

Participants must have presence of at least 1 measurable lesion on Baseline scan that will be confirmed by central radiology review. Participants must be considered resistant to the last administered platinum therapy, that is, the time from the last administered platinum dose until the initial documented progression as evidenced by radiographic progression per RECIST must be less than 6 months. Participants must have completed at least 1 but no more than 3 prior lines of therapy for advanced or metastatic ovarian cancer.

Neoadjuvant, adjuvant, and the combination of both will be considered as 1 line of therapy. Treatment with single-agent bevacizumab given as maintenance is not counted as a separate line of therapy. If a therapeutic regimen is modified or changed for a reason other than lack of response or PD such as allergic reaction, toxicity, or drug availability , this is not counted as a separate line of therapy. Participants must have been previously treated with platinum-based regimen, taxane agent s , and bevacizumab bevacizumab could be used as a single agent or in combination with another agent, in frontline therapy, as maintenance, or for treatment of recurrent disease.

Part 2B: Participants must have archival tumor tissue available that is formalin-fixed and paraffin-embedded. For participants who do not have archival tissue, a new biopsy must be performed to obtain a tissue sample prior to study treatment initiation.

For Cohort G, participant must provide formalin fixed paraffin embedded FFPE tumor tissue block s with sufficient tumor content as confirmed by the Sponsor's designated central laboratory during screening to enable, for example, measures of homologous recombination pathway defects and PD-L1 status. The use of slides created from paraffin-embedded tissue as opposed to FFPE blocks must be approved by the Sponsor.

Female participants must have a negative serum pregnancy test within 72 hours prior to the date of the first dose of study medication: unless they are of non-child bearing potential. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound, magnetic resonance imaging MRI or computed tomography CT scan.

Tubal ligation must be confirmed with medical records of the actual procedure. Female participants of childbearing potential must agree to use 1 highly effective form of contraception with their partner starting with the screening visit through days after the last dose of study therapy.

Participant has an adequate organ function. Participant has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell cancer SqCC of the skin that has undergone potentially curative therapy, or in situ cervical cancer.

Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent within 90 days myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study including obtaining informed consent.

Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through days after the last dose of study treatment. Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.

Participant has an active autoimmune disease that has required systemic treatment in the past 2 years i. Replacement therapy e. Use of inhaled steroids, local injection of steroids, and steroid eye drops are allowed.

Participant has as history of interstitial lung disease. Participant has not recovered i. Participant has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study drug.

Participant has received prior anti-cancer therapy chemotherapy, targeted therapies, radiotherapy, or immunotherapy within 21 days, or less than 5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter.

Participant has received a live vaccine within 14 days of planned start of study therapy. Participant has a known hypersensitivity to dostarlimab components or excipients. For Cohort G, participants will not be eligible if they meet the following criteria: Participants who experienced disease progression within 3 months as evidenced by radiographic progression per RECIST of first-line platinum therapy.

Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, might interfere with the participant's participation for the full duration of the study treatment, or is not in the best interest of the participant to participate.

Participant is immunocompromised. Participants with splenectomy are allowed. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Please refer to this study by its ClinicalTrials. More Information. Publications automatically indexed to this study by ClinicalTrials.

Safety, antitumor activity, and pharmacokinetics of dostarlimab, an anti-PD-1, in patients with advanced solid tumors: a dose-escalation phase 1 trial. Need steroid therapy, except physiological replacement therapy. Prior treatment with any immunotherapy, including tumor vaccine therapy, radium, checkpoint inhibitors and others.

Subjects with severe mental disorders. Subjects with other malignant tumors. Patients with ongoing or active infection. History of participation in other clinical studies within 3 months or treatment with any gene therapy product. Intolerant or allergic to cyclophosphamide or fludarabine. Subjects not appropriate to participate in this clinical study judged by investigators. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials. More Information. Castrate-Resistant Prostate Cancer. National Library of Medicine U. However, due to its long half-life and binding time with the target, it is easy to result in severe immune-related adverse reactions. Besides, mAb drugs are expensive, complex to produce, and difficult to store and transport. The combination of antibodies blocking PD1 and agonistic antibodies triggering the costimulatory receptor glucocorticoid induced tumor necrosis factor receptor GITR may further improve the therapeutic effect Wang et al.

Using the mouse colon cancer cell line MC38, Wang et al. Wang et al. They found that aPDL1-GEM scaffold induced an immunogenic tumor phenotype in mice bearing tumor, promoted immune-mediated tumor regression, and prevented tumor recurrence after primary resection Wang et al. Gao et al. Although immune checkpoint blocking therapy has achieved great success in clinic, the response rate of immunotherapy is still low Spranger et al. The majority of patients have no obvious response to the treatment or will remain resistant to it Andrews et al.

Despite the promising efficacy of immune checkpoint inhibitors, the majority of treated patients have had immune-related adverse events IAEs to varying degrees Reynolds et al.

Commonly reported IAEs include rash or pruritus, gastrointestinal disorders, and endocrine disorders Farolfi et al. Among these, cardiovascular toxicity is particularly severe. In recent years, reports of myocarditis associated with ICIs have increased Moslehi et al. Myocarditis associated with ICIs often manifests as arrhythmias and can coexist with myocarditis and myasthenia gravis, with severe disease and poor prognosis Hu et al. There is evidence that redox mechanisms are the main mechanism responsible for cardiotoxicity Tocchetti et al.

CTLA-4 is prone to immune-related adverse reactions such as rash, diarrhea, colitis, hepatotoxicity and endocrine disorders Hodi et al. Over the past 20 years since the discovery of PD1, numerous experimental studies have proved the clinical efficacy of PD1 blockers in a wide range of solid and hematologic malignancies, offering promising prospects for cancer patients Errico, In addition, reports based on the clinical application of PD1 inhibitors have elucidated the mechanism of tumor immune escape and confirmed the general significance of tumor immune monitoring and tumor immune editing Burnet, ; Schreiber et al.

Nevertheless, there is still a need for a large number of basic and exploratory studies on the prediction of tumor biomarkers, as well as the efficacy of drug therapy and adverse drug reactions. Due to the occurrence of drug resistance, the efficacy of immunosuppressive therapy is poor. We hope that future studies can minimize drug resistance, reduce the occurrence of immune-related adverse events and improve the efficacy of immunotherapy.

We believe that as research progresses, personalized immunotherapy will be further developed in the clinic to bring hope to cancer patients. JL summarized the literature and drafted the manuscript. YL and WZ provided revisions. All of them approve the final version and participate in the submission. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

National Center for Biotechnology Information , U. Front Pharmacol. Published online Sep 1. Author information Article notes Copyright and License information Disclaimer.

This article was submitted to Inflammation Pharmacology, a section of the journal Frontiers in Pharmacology. Received Jun 28; Accepted Aug The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Please refer to this study by its ClinicalTrials.

Layout table for location contacts Contact: Reinhard Dummer, Prof. University Hospital Zurich, Clinic of Dermatology. More Information. National Library of Medicine U. National Institutes of Health U. Department of Health and Human Services. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Basal Cell Carcinoma. Drug: Cemiplimab Injection [Libtayo]. Phase 2.

Study Type :. Interventional Clinical Trial. Estimated Enrollment :. Actual Study Start Date :. Estimated Primary Completion Date :. Estimated Study Completion Date :. Other Name: Sonidegib. Contact: Reinhard Dummer, Prof.