NCT05824975Phase 1, Phase 2Recruiting
GI Innovation, Inc. · Mayo Clinic in Arizona, Scottsdale, Arizona
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-102 as a single agent and in combination with conventional anti-cancer drugs, pembrolizumab or trastuzumab deruxtecan(T-DXd) over a range of advanced and/or metastatic solid tumors.
Eligibility: 18 Years to · All · Key
* Males and females aged ≥ 18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening.
* Has adequate organ and marrow function as defined in protocol.
* Measurable disease as per RECIST v1.1.
* ECOG performance status 0-1.
* Adverse events related to any prior chemotherapy, radiotherapy, immunotherapy, other prior systemic anti-cancer therapy, or surgery must have resolved to Grade ≤1, except alopecia and Grade 2 peripheral neuropathy.
* HIV infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease as defined in protocol.
Key
NCT05269381Phase 1, Phase 2Recruiting
Mayo Clinic · Mayo Clinic in Florida, Jacksonville, Florida
This phase I/II trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.
Eligibility: 16 Years to · All · Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.
PHASE I PRE-REGISTRATION, ALL:
* Willing to provide tissue specimens per protocol, or have clinically collected formalin-fixed paraffin-embedded (FFPE) tissue blocks, or available sequencing data available from commercial or research tests
* NOTE 1: Includes fresh tissue specimen at pre-registration, or with or clinically collected FFPE tissue blocks for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo IRB protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and/or registration.
* NOTE 2: This criteria will not apply to patients who had sequencing and neoantigen prediction previously completed.
* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
* NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy
* Provide written informed consent. For pediatric patients (age 16-17 years):
* Written informed consent from legal guardian(s) and/or child obtained in accordance with local regulations.
* Willing to return to enrolling institution for follow-up
* Willing to provide blood specimens for research
* Negative pregnancy test 7 days prior to pre-registration for persons of childbearing potential.
* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle
* Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior to pre-registration
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
* Anticipated life expectancy \> 6 months
* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).
* The following lab values obtained ≤ 28 days prior to pre-registration:
* Hemoglobin ≥ 9.0 g/dL (Must be ≥ 7 days after most recent transfusion)
* Absolute neutrophil count (ANC) ≥ 1500/mm\^3 or ≥ 1.5 X 10\^9/L
* Platelet count ≥ 100,000/mm\^3 or ≥ 100 X 10\^9/L (Must be ≥7 days after most recent transfusion)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN or ≤ 5 x ULN with liver metastases
* Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance must be ≥ 50 ml/min using Cockcroft-Gault formula
* International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy
PHASE I REGISTRATION, ALL:
* Successful sequencing and production of REAL-Neo vaccine
* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
* NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
* ECOG PS 0 or 1
* Anticipated life expectancy \> 6 months
* The following lab values obtained ≤ 14 days prior to registration:
* Hemoglobin ≥ 9.0 g/dl
* ANC ≥ 1500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 1.5 x ULN
* ALT and AST ≤ 3 x ULN (≤ 5 x ULN with liver involvement)
* PT/INR and aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy
* Calculated creatinine clearance ≥ 50 ml/min using Cockcroft-Gault formula
* Provide written informed consent
* Willing to provide blood and tissue sp
NCT07089992Phase 2Recruiting
Memorial Sloan Kettering Cancer Center · Memorial Sloan Kettering at Basking Ridge (All Protocol Activities), Basking Ridge, New Jersey
The purpose of the study is to find out if pembrolizumab is a useful treatment that causes few or mild side effects in people with ultra-rare sarcoma. The researchers will also study how the immune system responds to the study treatment.
Pembrolizumab is a type of drug called a PD-1 inhibitor. It is designed to block a protein called programmed cell death protein 1 (PD-1) that usually acts as a "brake" on the immune system. Blocking this protein is like releasing the brakes, so that the immune system can target cancer cells and destroy them.
Eligibility: 18 Years to · All · Inclusion:
* Patients must have pathologically confirmed diagnosis of one of the following:
1. Pleomorphic liposarcoma
2. PEComa (perivascular epithelial cell tumor)
3. Epithelioid sarcoma
4. CIC-rearranged sarcoma
5. SEF/LGFMS: Sclerosing epithelioid fibrosarcoma - low grade fibromyxoid sarcoma
* Molecular characterization of the tumor, if available, will be recorded. If no such molecular data are available, note as such.
* Patient should have recurrent or metastatic disease not judged to be curable with other means
* Patients must have progressed (in the opinion of the treating investigator) following the most recent line of therapy or stop prior therapy due to toxicity or patient choice. The reason for this progression or other reason for changing therapy must be documented, employing tumor measurements when available.
* Definition of Measurable Disease
* Measurable disease as per RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions for a minimum of 3 months after completion of such therapy
* Patients with treated brain metastases are eligible if follow up brain imaging after CNS-directed therapy shows no evidence of progression at least 4 weeks after the completion of therapy as shown by follow up imaging before study screening
* One to 3 prior lines of therapy are permitted (including neoadjuvant/adjuvant or metastatic/recurrent disease)
* Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible. Patients with alopecia and other toxicities considered clinically nonsignificant and/or stable on supportive therapy, as determined by the investigator, are also permitted on study.
* Administration of killed vaccines is allowed
* Age ≥ 18 years of age.
* ECOG Performance Status 0-1 (Karnofsky 70-100)
* Required organ function (specimens to be collected within 14 days of the start of the study intervention)
* Adequate hematologic function, defined as:
* Absolute neutrophil count (ANC) ≥ 1,000 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 9 g/dl
* Adequate renal function defined, as:
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert disease who have bilirubin level ≤ 3 x ULN may be enrolled)
* AST and ALT ≤3 x institutional ULN
* Adequate cardiac function, defined as: class II or better New York Heart Association (NYHA) Functional Classification.
* For patients with known HIV, HBV, and/or HCV infection \[HIV, HBV, and HCV testing do not need to be performed as part of the study; the below language provides guidelines for inclusivity of patients with known HIV, HBV, and/or HCV infection\]:
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and CD4+ T cell count of at least 350 cell/mm3 are eligible for this trial.
* HIV-infected patients with a history of either Kaposi sarcoma or Castleman disease are excluded from this study
* HIV-infected patients must not have had an AIDS defining opportunistic infection within the past 12 months
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Exclusion:
* No prior diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug.
* No
NCT03556228Phase 1, Phase 2Recruiting
VM Oncology, LLC · Providence Medical Foundation (site 209), Santa Rosa, California
This is a multicenter, open-label, Phase 1/2 study of orally administered VMD-928 monotherapy and in combination with pembrolizumab in adult subjects with advanced solid tumors or lymphoma that have progressed or are non responsive to available therapies and for which no standard or available curative therapy exists
Eligibility: 18 Years to 80 Years · All · Key
#. Histologically or cytologically confirmed diagnosis of any type of solid tumor malignancy or lymphoma:
Phase 1 Dose Escalation only: Subjects with
(A) any advanced solid tumors of
1. Head and Neck Cancers ("HNC") (of any types),
2. Esophageal cancer,
3. Lung cancers (of any types),
4. Mesothelioma,
5. Pancreatic cancers,
Or,
(B) any NTRK1 gene fusion positive ("NTRK1+") solid tumors or lymphomas, that is relapsed, refractory or intolerant (R/R/I) to standard of care (SOC) and for which there is no approved or curative therapy. Additionally, patients must not be candidates for or have exhausted regimens known to provide clinical benefit, including hematopoietic stem cell transplantation in lymphoma patients if they are deemed transplant eligible.
Phase 2 Monotherapy and Combination with Pembrolizumab only:
Subjects must have
1. TrkA-driven HNC, Esophageal, Lung, Mesothelioma, Pancreatic cancers; or,
2. any NTRK1+ solid tumors or lymphoma\*, that is R/R/I to SOC.
Key Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1.
* Able to swallow and retain oral medication.
* Subjects must either have available archival tumor tissue samples, or consent to tumor tissue sampling prior to the first dose.
* Adequate organ system function as defined as follows:
1. Absolute neutrophil count ≥1.5x10\^9/L
2. Hemoglobin ≥9g/dL
3. Platelets ≥100x10\^9/L
4. PT/INR, PTT ≤1.5xULN
5. Total bilirubin ≤1.5x ULN
6. AST, ALT ≤2.5xULN
7. Creatinine ≤1.2xULN for age, weight
8. Calculated creatinine clearance or 24h urine creatinine clearance ≥60mL/min
Key
NCT05784688Phase 1, Phase 2Recruiting
TiumBio Co., Ltd. · NEXT Oncology, San Antonio, Texas
This study consists of phase 1b and 2a to evaluate safety, Pharmacokinetics, and efficacy of TU2218 in combination with Pembrolizumab in patients with advanced solid tumors.
Eligibility: 18 Years to · All · 1. Male and females ≥18 years of age
2. Life expectancy ≥12 weeks as judged by the Investigator
3. Measurable disease as defined by RECIST v1.1
4. ECOG 0 or 1
5. Able to swallow capsules
6. For Phase 1b and 2a: histologically or cytologically documented advanced unresectable solid tumor for which no effective standard therapy exists, or that has progressed on or not tolerated prior standard therapy. If previously treated with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies, PD-1 treatment progression is defined by meeting all of the following criteria:
1. Has received at least 2 doses of an approved anti-PD-1/L1 mAb
2. Has demonstrated clinical progression after anti-PD-1/L1 mAb therapy
3. Progressive disease has been documented within 16 weeks from the last dose of anti-PD-1/L1 mAb
7. For HNSCC cohort in Phase 2a: anti-PD-(L)1 agent-naïve metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC) whose tumors express programmed death ligand 1 (PD - L1) \[combined positive score (CPS) ≥1\] as determined by an FDA-approved test Or recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy (as applicable).
8. For BTC cohort in Phase 2a: biliary tract cancer that has been locally advanced unresectable or metastatic or not tolerated prior standard first line chemotherapy and second line targeted therapy (as applicable).
9. For CRC cohort in Phase 2a: anti-PD-(L)1 agent-naïve colorectal adenocarcinoma of Proficient Mismatch Repair (pMMR)/Microsatellite Stable (MSS) subtype, as determined by an FDA-approved test, that has progressed on or not tolerated at least 2 lines of prior standard chemotherapy with biological agents where applicable. Patients with liver metastasis from primary CRC, as confirmed by RESIST v1.1, will be excluded from Phase 2a CRC cohort.
10. Adequate hematological function and coagulation defined by
* ANC ≥1,500 cells/μL
* Platelet count ≥100,000/μL
* Hemoglobin ≥9.0 g/dL (criteria must be met without packed red blood cell transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin \[≥ approximately 3 months\])
* International normalized ratio ≤1.5 upper limit of normal (ULN)
11. Adequate hepatic and renal function
* Total bilirubin ≤1.5 × ULN
* AST and alanine aminotransferase (ALT) ≤2.5 × ULN; if liver metastases are present, then ≤5 × ULN is allowed.
* Estimated creatinine clearance ≥60 mL/minute according to the Cockcroft Gault formula.
12. Able to understand and to comply with all protocol requirements, instructions, and restrictions. For Phase 2a, willing and able to provide archival tumor samples or undergo biopsy for biomarker testing during screening.
13. QTcF interval ≤470 msec on screening ECG.
14. Normal ejection fraction (within the reference range of the institution).
15. No concomitant anti-cancer treatments, including experimental agents for 5 half-lives for non-biological agents and a minimum of 4 weeks for any biologics prior to the start of treatment.
16. Resolution of any toxicity to maximum Grade 1 (except alopecia and Grade ≤2 neuropathy) prior to the start of treatment. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement are eligible.
17. Completion of radiotherapy (palliative or curative) at least 14 days prior to the start of treatment with resolution of any toxicity to maximum Grade 1. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
18. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) defined as all female after puberty unless they are postmenopausal for at least 1 year or are surgically st
NCT06901531Phase 3Recruiting
Astellas Pharma Global Development, Inc. · UAB Medicine - UAB Hospital, Birmingham, Alabama
Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called gastroesophageal junction (GEJ) cancer. Zolbetuximab with chemotherapy may be used to treat stomach and GEJ cancer when the cancer cells do not have a protein called HER2 (human epidermal growth factor receptor 2) on their surface (HER2-negative) but do have a protein called Claudin 18.2 (Claudin 18.2-positive). Zolbetuximab is thought to work by attaching to the Claudin 18.2 protein in their tumor, which switches on the body's immune system to attack the tumor. Certain stomach and GEJ cancers may be treated with immunotherapy, which helps the body's immune system fight cancer. This study will give more information about how well zolbetuximab works when given with an immunotherapy medicine called pembrolizumab and chemotherapy. In this study, adults with stomach cancer or GEJ cancer will either be given zolbetuximab with pembrolizumab and chemotherapy or a placebo with pembrolizumab and chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it.
The main aim of the study is to check how long people with stomach cancer and GEJ cancer live after treatment with zolbetuximab with pembrolizumab and chemotherapy compared to placebo with pembrolizumab and chemotherapy.
Adults with locally advanced unresectable or metastatic stomach cancer or GEJ cancer can take part. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. A tumor sample (biopsy) of their cancer will have the Claudin 18.2 protein, PD-L1 protein, and be HER2-negative. They may have been previously treated with certain standard therapies. People can also take part if they need to take medicines like steroids to suppress their immune system. They cannot take part if they have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, or have a specific heart condition, or infections.
The study treatments are either zolbetuximab with pembrolizumab and chemotherapy, or placebo with pembrolizumab and chemotherapy. People who take part will receive just 1 of the study treatments by chance. The people in the study and the study doctors will not know who takes which of the study treatments. Study treatment will be given in 6-week (42-day) cycles. The study treatment is mainly given to people slowly through a tube into a vein. This is called an infusion. People will receive study treatment as follows: Zolbetuximab or placebo: 1 infusion every 2 or 3 weeks (2 or 3 infusions in a cycle) together with: Chemotherapy (1 of the following types of chemotherapy): 1. CAPOX (capecitabine and oxaliplatin): 1 infusion of oxaliplatin every 3 weeks (2 infusions in a cycle). People will also take 1 tablet of capecitabine twice a day for 2 weeks (14 days) at the start of each cycle (Day 1) and again in the middle of each cycle (Day 22). After 8 study treatments people will receive capecitabine only. 2. Modified FOLFOX6 or mFOLFOX6 (5-fluorouracil, folinic acid and oxaliplatin): 1 infusion every 2 weeks (3 infusions in a cycle). After 12 study treatments people will receive folinic acid and fluorouracil only, instead of mFOLFOX6. Pembrolizumab: 1 infusion every 3 or 6 weeks (1 or 2 infusions in a cycle). People can be in the study and will receive study treatment until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People may receive pembrolizumab for up to 2 years. People will visit the clinic on certain days to receive their study treatment and have health checks. The study doctors will check if people had any medical problems from taking zolbetuximab or the other study treatments. On some visits they will have scans to check for any changes in their cancer. People will have the option of giving a tumor sample if they stop treatment because their cancer has worsened. People will visit the clinic after they stop their study treatment. People will be asked about any medical problems and will have a health check. People will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. They will have telephone health checks every 3 months. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their study treatment or not.
Eligibility: 18 Years to · All · * Participant has histologically confirmed gastric or Gastroesophageal Junction (GEJ) adenocarcinoma.
* Participant has radiographically confirmed, locally advanced, unresectable or metastatic disease within 28 days prior to randomization.
* Participant has radiologically evaluable disease (measurable and/or nonmeasurable) according to Response Evaluation Criteria in Solid Tumors (RECIST) V1.1, ≤ 28 days prior to randomization. For participants with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
* Participant has Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0 to 1.
* Participant has predicted life expectancy ≥ 12 weeks.
* Participant must be a candidate to receive mFOLFOX6 or CAPOX and pembrolizumab.
* Female participant is not pregnant and at least 1 of the following conditions apply:
* Not a woman of child bearing potential (WOCBP)
* WOCBP who has a negative urine or serum pregnancy test at screening (Specific to Japan: with a medical interview), and agrees to follow the contraceptive guidance from the time of informed consent through at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study interventions.
* Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 5 half-lives (at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study interventions).
* Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period, and for 9 months after the final administration of oxaliplatin and for 6 months after final administration of all other study interventions.
* Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period, and for 6 months after final investigational study intervention administration.
* Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 6 months after the final investigational study intervention administration.
* Male participant must not donate sperm during the treatment period and for 6 months after the final investigational study intervention administration
* Participant has a Human Epidermal Growth Factor Receptor 2 (HER2) -negative tumor.
* Participant's tumor expresses Claudin18.2 (CLDN18.2) in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing.
* Participant's tumor expresses Programmed death ligand (PD-L1) combined positive score (CPS) ≥ 1 as determined by central IHC testing.
* Participants with known microsatellite instability-high or mismatch repair deficient status may enroll as long as they meet the PD-L1 positivity criteria.
* Participant must meet all of the criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In case of multiple central laboratory data within this period, the most recent data should be used.
* Participant agrees not to participate in another interventional study while receiving study intervention in the present study.
NCT05185739Phase 2Recruiting
University College, London · Queen Elizabeth Hospital, Birmingham
This is a multicentre randomised 3-arm phase II clinical trial in patients with resectable Hepatocellular Carcinoma (HCC). Sixty patients will be randomized 1:1:1 to 6 weeks of pre-operative therapy with: pembrolizumab, lenvatinib or the combination of pembrolizumab and lenvatinib followed by up to 12 months treatment with post-operative pembrolizumab. The aim of the study is to compare the efficacy of pembrolizumab combined with lenvatinib with that of pembrolizumab and lenvatinib alone in terms of major pathological response in patients with resectable HCC. Major pathological response will be defined by the proportion of patients with less than 10% viable tumour at resection.
Eligibility: 18 Years to · All · 1. Have a diagnosis of Hepatocellular Carcinoma (HCC) confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) and suitable for surgical resection. Radiological confirmation of diagnosis is provided by the study site and defined by the presence of a liver mass of at least 1 cm and exhibiting arterial hypervascularity with washout in the portal venous phase seen in a tri-phasic magnetic resonance imaging (MRI).
2. Measurable disease based on RECIST 1.1
3. HCC amenable to R0 resection with curable intent
4. Child-Pugh A liver disease
5. International normalised ratio (INR) ≤1.4
6. ECOG Performance status 0 or 1
7. Adequate haematological function as defined by:
* Haemoglobin (Hb) \> 90g/l
* Neutrophil Count \> 1.5 x 109/l
* Platelets \> 75 x 109/l
8. Adequate renal function with GFR \>40ml/min using a validated creatinine clearance calculation (e.g. Cockcroft-Gault or Wright formula)
9. Adequate liver function as defined by:
* Aminotransferase (ALT) or aspartate aminotransferase (AST) \< 5.0 x ULN
* Albumin \>32g/l
* Amylase ≤ 1.5 x ULN
10. Patients with past or ongoing hepatitis C virus (HCV) infection will be eligible for the study if HCV viral load is undetectable at screening. The treated patients must have completed their treatment curative anti-viral treatment at least 4 weeks prior to randomisation.
11. Patients with controlled hepatitis B will be eligible as long as they meet the following criteria:
* Antiviral therapy for hepatitis B virus (HBV) must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL prior to randomisation. Patients on active HBV therapy with viral loads under 500 IU/mL should stay on the same therapy throughout study treatment.
* Patients who are positive for anti-hepatitis B core antibody (HBc), negative for hepatitis B surface antigen (HBsAg), and negative or positive for anti-hepatitis B surface antibody (HBs), and who have an HBV viral load under 500 IU/mL, do not require HBV anti-viral prophylaxis
12. 18 years of age or over
13. Predicted life expectancy of \> 3 months
14. Patients must have given written informed consent
15. Patients must have the ability to swallow oral medication
16. Must be willing to use effective contraception during study for 120 days after last dose.
NCT06265025Phase 1, Phase 2Recruiting
GeneMedicine Co., Ltd. · National Cancer Center, Goyang-si, Gyeonggi-do
The purpose of this study is to measure safety, tolerability, and preliminary antitumor efficacy of GM103 administered alone and in combination with pembrolizumab in patients with locally advanced, unresectable, refractory and/or metastatic solid tumors (including but not limited to head and neck cancer, malignant melanoma, CRC, renal cell carcinoma, cervical cancer, and breast cancer). Study details include:
Eligibility: 18 Years to · All · 1. Patient must be 18 years of age or over, at the time of signing the informed consent.
2. Have a diagnosis of locally advanced, unresectable, refractory and/or metastatic solid tumors
3. Have a tumor that is accessible and is willing to consent to tumor biopsies during the study.
4. Have at least one measurable site of disease according to RECIST 1.1 criteria; The lesions should be either previously non irradiated or progressive lesions after irradiation, that can be accurately measured at baseline (for measurable lesions) with computed tomography (CT) or magnetic resonance imaging (MRI).
5. Part A, B and C: Have at least one intratumorally injectable lesion (measurable and/or non-measurable based on RECIST 1.1), that can be accurately measured at baseline (for measurable lesions) with computed tomography (CT) or magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT); or clinical examination and which is suitable for repeated measurement.
6. Part B and C (only for dose expansion cohort): Have paired pre- and on treatment tumor biopsies for patients with metastases that are safely accessible as determined by the investigator.
7. Patients with brain metastasis must have stable disease and must be neurologically asymptomatic and not requiring corticosteroid treatment.
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
9. Have a predicted life expectancy of 12 weeks or more.
10. Able to comply with study procedures in the Investigator's opinion.
11. Adequate organ function determined within 4 weeks prior to screening
12. Patient is male or female.
13. Contraceptive use by women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
14. Patient is capable of giving signed informed consent.
NCT05824975Phase 1, Phase 2Recruiting
GI Innovation, Inc. · Mayo Clinic in Arizona, Scottsdale, Arizona
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-102 as a single agent and in combination with conventional anti-cancer drugs, pembrolizumab or trastuzumab deruxtecan(T-DXd) over a range of advanced and/or metastatic solid tumors.
Eligibility: 18 Years to · All · Key
* Males and females aged ≥ 18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening.
* Has adequate organ and marrow function as defined in protocol.
* Measurable disease as per RECIST v1.1.
* ECOG performance status 0-1.
* Adverse events related to any prior chemotherapy, radiotherapy, immunotherapy, other prior systemic anti-cancer therapy, or surgery must have resolved to Grade ≤1, except alopecia and Grade 2 peripheral neuropathy.
* HIV infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease as defined in protocol.
Key
NCT05269381Phase 1, Phase 2Recruiting
Mayo Clinic · Mayo Clinic in Florida, Jacksonville, Florida
This phase I/II trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.
Eligibility: 16 Years to · All · Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.
PHASE I PRE-REGISTRATION, ALL:
* Willing to provide tissue specimens per protocol, or have clinically collected formalin-fixed paraffin-embedded (FFPE) tissue blocks, or available sequencing data available from commercial or research tests
* NOTE 1: Includes fresh tissue specimen at pre-registration, or with or clinically collected FFPE tissue blocks for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo IRB protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and/or registration.
* NOTE 2: This criteria will not apply to patients who had sequencing and neoantigen prediction previously completed.
* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
* NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy
* Provide written informed consent. For pediatric patients (age 16-17 years):
* Written informed consent from legal guardian(s) and/or child obtained in accordance with local regulations.
* Willing to return to enrolling institution for follow-up
* Willing to provide blood specimens for research
* Negative pregnancy test 7 days prior to pre-registration for persons of childbearing potential.
* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle
* Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior to pre-registration
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
* Anticipated life expectancy \> 6 months
* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).
* The following lab values obtained ≤ 28 days prior to pre-registration:
* Hemoglobin ≥ 9.0 g/dL (Must be ≥ 7 days after most recent transfusion)
* Absolute neutrophil count (ANC) ≥ 1500/mm\^3 or ≥ 1.5 X 10\^9/L
* Platelet count ≥ 100,000/mm\^3 or ≥ 100 X 10\^9/L (Must be ≥7 days after most recent transfusion)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN or ≤ 5 x ULN with liver metastases
* Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance must be ≥ 50 ml/min using Cockcroft-Gault formula
* International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy
PHASE I REGISTRATION, ALL:
* Successful sequencing and production of REAL-Neo vaccine
* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
* NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
* ECOG PS 0 or 1
* Anticipated life expectancy \> 6 months
* The following lab values obtained ≤ 14 days prior to registration:
* Hemoglobin ≥ 9.0 g/dl
* ANC ≥ 1500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 1.5 x ULN
* ALT and AST ≤ 3 x ULN (≤ 5 x ULN with liver involvement)
* PT/INR and aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy
* Calculated creatinine clearance ≥ 50 ml/min using Cockcroft-Gault formula
* Provide written informed consent
* Willing to provide blood and tissue sp
NCT06929286Phase 3Recruiting
Memorial Sloan Kettering Cancer Center · Johns Hopkins University (Data Collection Only), Baltimore, Maryland
The purpose of this study is to compare the effectiveness of different FDA-approved/NCCN-recommended drug treatments for NMIBC. In particular, the FDA-approved drug nadofaragene firadenovec will be compared to usual care with other NCCN-recommended standard treatments for NMIBC (gemcitabine with or without docetaxel, mitomycin, re-treatment with BCG, or pembrolizumab).
Eligibility: 21 Years to · All · * 21 years of age or older
* Being treated for high-grade NMIBC (Tis, Ta, or T1) under the care of the participating treating urologists
* One or more prior induction course of BCG at any point in time and judgment by the treating urologist that BCG has failed
°Any amount of maintenance BCG is allowed
* In the previous 12 months, receipt of at least one instillation of any intravesical agent (induction or maintenance) or one administration of systemic therapy for NMIBC treatment
* An intravesical agent can include BCG or any other NMIBC treatment
* Up to 15 months from the last instillation is allowed for the treating physician to perform a transurethral resection of bladder tumor (TURBT) so long as there is evidence/suspicion of recurrent disease (by urinary cytology, imaging, or cystoscopy) within 12 months of last exposure to an intravesical agent.
* In the opinion of the treating urologist, there is no contraindication to treatment with nadofaragene firadenovec (i.e. hypersensitivity to IFNa, severe immunosuppression) and there is uncertainty over whether nadofaragene is better than "best usual care"
NCT03556228Phase 1, Phase 2Recruiting
VM Oncology, LLC · Providence Medical Foundation (site 209), Santa Rosa, California
This is a multicenter, open-label, Phase 1/2 study of orally administered VMD-928 monotherapy and in combination with pembrolizumab in adult subjects with advanced solid tumors or lymphoma that have progressed or are non responsive to available therapies and for which no standard or available curative therapy exists
Eligibility: 18 Years to 80 Years · All · Key
#. Histologically or cytologically confirmed diagnosis of any type of solid tumor malignancy or lymphoma:
Phase 1 Dose Escalation only: Subjects with
(A) any advanced solid tumors of
1. Head and Neck Cancers ("HNC") (of any types),
2. Esophageal cancer,
3. Lung cancers (of any types),
4. Mesothelioma,
5. Pancreatic cancers,
Or,
(B) any NTRK1 gene fusion positive ("NTRK1+") solid tumors or lymphomas, that is relapsed, refractory or intolerant (R/R/I) to standard of care (SOC) and for which there is no approved or curative therapy. Additionally, patients must not be candidates for or have exhausted regimens known to provide clinical benefit, including hematopoietic stem cell transplantation in lymphoma patients if they are deemed transplant eligible.
Phase 2 Monotherapy and Combination with Pembrolizumab only:
Subjects must have
1. TrkA-driven HNC, Esophageal, Lung, Mesothelioma, Pancreatic cancers; or,
2. any NTRK1+ solid tumors or lymphoma\*, that is R/R/I to SOC.
Key Inclusion Criteria:
* Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1.
* Able to swallow and retain oral medication.
* Subjects must either have available archival tumor tissue samples, or consent to tumor tissue sampling prior to the first dose.
* Adequate organ system function as defined as follows:
1. Absolute neutrophil count ≥1.5x10\^9/L
2. Hemoglobin ≥9g/dL
3. Platelets ≥100x10\^9/L
4. PT/INR, PTT ≤1.5xULN
5. Total bilirubin ≤1.5x ULN
6. AST, ALT ≤2.5xULN
7. Creatinine ≤1.2xULN for age, weight
8. Calculated creatinine clearance or 24h urine creatinine clearance ≥60mL/min
Key
