NCT05005403Phase 1Recruiting
AbbVie · City of Hope National Medical Center /ID# 276272, Duarte, California
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. Head and Neck Squamous Cell Carcinoma (HNSCC) is a solid tumor, a disease in which cancer cells form in the tissues of the head and neck. The purpose of this study is to assess adverse events and pharmacokinetics of azirkitug as a monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan.
Bevacizumab is an approved product, while budigalimab, azirkitug, and telisotuzumab adizutecan are investigational drugs being developed for the treatment of NSCLC, HNSCC, and other solid tumors. Study doctors put the participants in groups called treatment arms. The maximum-tolerated dose (MTD)/maximum administered dose (MAD) of azirkitug will be explored. Each treatment arm receives a different dose of azirkitug in monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan. Approximately 694 adult participants will be enrolled in the study across approximately 80 sites worldwide.
Participants will receive azirkitug as a monotherapy or in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan as an Intravenous (IV) Infusion for an estimated treatment period of up to 2 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Eligibility: 18 Years to · All · * Pre Treatment biopsy or archive tissue within 6 months without intervening treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of \<= 0 or 1 and a life expectancy of \>= 3 months.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
* Laboratory values meeting criteria outlined in the protocol
* NSCLC - Advanced or metastatic progressed on standard of care (SOC) including chemotherapy and prior anti-PD-(L)1 antibody (separately or in combination). Actionable gene alterations are eligible if failed targeted therapeutic options.
* HSNCC - Advanced/metastatic progressed on platinum and PD-1/PD-LI in recurrent or metastatic setting.
* Micro Satellite Stable Colorectal Cancer (MSS-CRC) - Progressed on Oxaliplatin, Irinotecan, a fluoropyrimidine, anti-EGFR, VEGF or VEGFR therapies, BRAFV600E or HER2, other targetable mutations targeted with locally approved therapy, TAS-102, Regorafenib and not MSI-h or MMR-deficient
* Gastric and Gastroesophageal Junction adenocarcinoma (GEA) - Advanced/metastatic progressed on at least 1 prior cytotoxic chemotherapeutic regimen and if applicable immune checkpoint inhibitor and/or HER2 therapy
* High-Grade Serous Ovarian Cancer (HGSOC) - Progressed serous epithelial ovarian, fallopian tube or primary peritoneal cancer post SOC and not eligible for surgical resection. Platinum resistant cannot have \>5 lines of prior therapy.
* Pancreatic Adenocarcinoma (PDAC) - Advanced/metastatic progressed after SOC. Includes adenosquamous carcinoma and post-Whipple.
* Triple Negative Breast Cancer (TNBC) - Progressed after 1 or 2 systemic therapy that must have included taxane and treatment naïve to immunotherapy targeting T-cell co-stimulation
NCT05005403Phase 1Recruiting
AbbVie · City of Hope National Medical Center /ID# 276272, Duarte, California
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. Head and Neck Squamous Cell Carcinoma (HNSCC) is a solid tumor, a disease in which cancer cells form in the tissues of the head and neck. The purpose of this study is to assess adverse events and pharmacokinetics of azirkitug as a monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan.
Bevacizumab is an approved product, while budigalimab, azirkitug, and telisotuzumab adizutecan are investigational drugs being developed for the treatment of NSCLC, HNSCC, and other solid tumors. Study doctors put the participants in groups called treatment arms. The maximum-tolerated dose (MTD)/maximum administered dose (MAD) of azirkitug will be explored. Each treatment arm receives a different dose of azirkitug in monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan. Approximately 694 adult participants will be enrolled in the study across approximately 80 sites worldwide.
Participants will receive azirkitug as a monotherapy or in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan as an Intravenous (IV) Infusion for an estimated treatment period of up to 2 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Eligibility: 18 Years to · All · * Pre Treatment biopsy or archive tissue within 6 months without intervening treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of \<= 0 or 1 and a life expectancy of \>= 3 months.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
* Laboratory values meeting criteria outlined in the protocol
* NSCLC - Advanced or metastatic progressed on standard of care (SOC) including chemotherapy and prior anti-PD-(L)1 antibody (separately or in combination). Actionable gene alterations are eligible if failed targeted therapeutic options.
* HSNCC - Advanced/metastatic progressed on platinum and PD-1/PD-LI in recurrent or metastatic setting.
* Micro Satellite Stable Colorectal Cancer (MSS-CRC) - Progressed on Oxaliplatin, Irinotecan, a fluoropyrimidine, anti-EGFR, VEGF or VEGFR therapies, BRAFV600E or HER2, other targetable mutations targeted with locally approved therapy, TAS-102, Regorafenib and not MSI-h or MMR-deficient
* Gastric and Gastroesophageal Junction adenocarcinoma (GEA) - Advanced/metastatic progressed on at least 1 prior cytotoxic chemotherapeutic regimen and if applicable immune checkpoint inhibitor and/or HER2 therapy
* High-Grade Serous Ovarian Cancer (HGSOC) - Progressed serous epithelial ovarian, fallopian tube or primary peritoneal cancer post SOC and not eligible for surgical resection. Platinum resistant cannot have \>5 lines of prior therapy.
* Pancreatic Adenocarcinoma (PDAC) - Advanced/metastatic progressed after SOC. Includes adenosquamous carcinoma and post-Whipple.
* Triple Negative Breast Cancer (TNBC) - Progressed after 1 or 2 systemic therapy that must have included taxane and treatment naïve to immunotherapy targeting T-cell co-stimulation
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
NCT06529822Phase 1Recruiting
Washington University School of Medicine · AdventHealth, Orlando, Florida
This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine strategy in patients with solid tumors and molecular residual disease. The hypothesis of the trial is that synthetic long peptide personalized cancer vaccines will be safe and capable of generating measurable neoantigen-specific T-cell responses enabling ctDNA clearance. The personalized cancer vaccines are composed of synthetic long peptides corresponding to prioritized cancer neoantigens and will be co-administered with poly-ICLC.
Eligibility: 18 Years to · All · Inclusion Criteria Cohort #1:
* Age ≥ 18 years.
* ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
* Histologically confirmed muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (renal pelvis and/or ureter).
* Patients with carcinomas showing mixed histologies are required to have a dominant transitional cell pattern.
* Complete surgical resection of MIBC (R0) or upper tract urothelial carcinoma (renal pelvis and/or ureter). Tumor, nodes, metastases (TNM) classification (based on the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th ed.) at pathological examination of surgical resection specimen as follows: ypT0N0M0, pT2-4N0M0, or pT0-4aN+M0.
* Patient must have fully recovered from surgical resection in the opinion of the treating MD.
* ctDNA positive result as identified by Signatera.
* Radiologic confirmation (by conventional imaging) of absence of residual disease and absence of metastasis.
* Adequate bone marrow and organ function as defined below:
* WBC ≥ 1.5 K/cumm
* Absolute neutrophil count ≥ 1.0 K/cumm
* Platelets ≥ 50 K/cumm
* Hemoglobin ≥ 8.0 g/dL
* Total bilirubin ≤ 1.5 x IULN
* AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
* Creatinine clearance \> 30 mL/min by Cockcroft-Gault
* The effects of synthetic long peptide personalized cancer vaccines and Hiltonol on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 5 months after completion of study interventions. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
* No concurrent investigational therapies outside of this protocol are allowed.
* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria Cohort #1:
* Receiving any other investigational agents, or planning to receive other investigational agents as part of neoadjuvant therapy. Patients who have received perioperative neoadjuvant chemotherapy and immunotherapy, including enfortumab vedotin plus pembrolizumab (EV+P), are allowed.
* Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
* A psychiatric illness or social situations that would limit compliance with study requirements as determined by the investigator from the medical history, physical exam, and/or medical record.
* Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. In the case of asthma or chronic obstructive pulmonary disease taking inhaled corticosteroids that does not require daily systemic corticosteroids is acceptable. Additionally, local acting steroids (topical, inhaled, or intraarticular) will be allowed. Patients on intermittent or short course steroids will be allow if the dose does not exceed 4 mg of dexamethasone (or equivalent) per day for \> 7 consecutive days. Premedication for chemotherapy does not apply to this criterion and may be administered as per SOC practice. Any patients receiving steroids should be discussed with the PI to determine if eligible.
* Known HIV-positive status.
* History of positive test for Hep
NCT07198165Phase 2Recruiting
Ruijin Hospital · Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai
This study aims to evaluate the efficacy and safety of short-course radiotherapy combined with CAPOX plus bevacizumab with or without a PD-1 inhibitor in patients with locally advanced rectal cancer (LARC). The hypothesis is that the addition of immunotherapy (PD-1 inhibitor) can significantly improve the complete response (CR) rate and enhance local control while reducing the incidence of distant metastasis. This study will compare the effects of sequential chemoradiotherapy and targeted therapy with or without immunotherapy following short-course radiotherapy, aiming to explore the optimal regimen for total neoadjuvant therapy.
Eligibility: 18 Years to 75 Years · All · * Histopathologically confirmed rectal adenocarcinoma with no prior antitumor therapy.
* Exclusion of patients with BRAF mutations or MSI-H status, as determined by pre-enrollment genetic testing including RAS, BRAF, and MSI analysis. RAS mutation status is permitted regardless.
* Absence of severe intestinal obstruction symptoms and no evidence of distant metastasis confirmed by imaging examinations such as CT, MRI, or PET/CT.
* Confirmation as locally advanced rectal cancer by rectal MRI, meeting one or more of the following criteria: T3c-d or T4, N2, EMVI(+), MRF(+), lateral lymph node metastasis; or patients with low-lying rectal cancer (≤5 cm from the anal verge) unsuitable for sphincter-preserving surgery prior to neoadjuvant therapy.
* Age 18 to 75 years.
* ECOG Performance Status of 0 to 1, without severe comorbid medical conditions.
* Adequate organ function:
Hematopoietic: Hemoglobin ≥90 g/L, Platelets ≥80 × 10\^9/L, Absolute Neutrophil Count ≥1.5 × 10\^9/L.
Hepatic: ALT and AST \< 2.5 × ULN. Renal: Serum Creatinine \< 1.5 × ULN.
* Provision of signed and dated written informed consent.
NCT05806931Phase 2Recruiting
Rutgers, The State University of New Jersey · Trinitas Hospital and Comprehensive Cancer Center, Elizabeth, New Jersey
This study is to evaluate the disease control rate and time to progression of the sequential combination of oxaliplatin with an alternative anti-metabolite Trifluridine/tipiracil hydrochloride mixture, TAS-102,(TAS-OX) as well as irinotecan in combination with TAS-102 oxaliplatin(TAS-OX) + Bevacizumab in late-line metastatic colorectal cancer (mCRC)
Eligibility: 18 Years to · All · * Histologically confirmed stage IV colon cancer (AJCC 7th edition) that has progressed after standard therapy that included 5-FU, irinotecan, oxaliplatin and appropriate antibody therapy. Antibody therapy with bevacizumab and an anti-EGFR antibody, if RAS wild type, should have been given unless medical reasons have precluded their use. Participants who could not tolerate standard agents because of unacceptable, but reversible toxicity necessitating their discontinuation will be allowed to participate.
* Participants who had received adjuvant chemotherapy and had recurrence during or within six months of completion of the adjuvant chemotherapy will be allowed to count the adjuvant therapy as one chemotherapy regimen for advanced disease.
* Progression of disease must be documented on the most recent scan.
* Presence of measurable disease
* RAS mutation and MMR status must be determined (or tissue availability for testing if not already determined).
* Age 18 years or older.
* ECOG performance status 0-1.
* Life expectancy of at least three months.
* Participants with adequate organ function:
1. Absolute neutrophil count (ANC) \> 1.5 x 109/L
2. Hemoglobin \> 9 g/dL
3. Platelets (PLT) \> 70 x 109/L
4. AST/ALT \< 5 x ULN
5. Albumin within normal limits for institution
* Women who are nursing and discontinue nursing prior to enrollment in the program.
* Ability to take oral medication (i.e., no feeding tube).
* Participant able and willing to comply with study procedures as per protocol.
* Participant able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures.
NCT05005403Phase 1Recruiting
AbbVie · City of Hope National Medical Center /ID# 276272, Duarte, California
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. Head and Neck Squamous Cell Carcinoma (HNSCC) is a solid tumor, a disease in which cancer cells form in the tissues of the head and neck. The purpose of this study is to assess adverse events and pharmacokinetics of azirkitug as a monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan.
Bevacizumab is an approved product, while budigalimab, azirkitug, and telisotuzumab adizutecan are investigational drugs being developed for the treatment of NSCLC, HNSCC, and other solid tumors. Study doctors put the participants in groups called treatment arms. The maximum-tolerated dose (MTD)/maximum administered dose (MAD) of azirkitug will be explored. Each treatment arm receives a different dose of azirkitug in monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan. Approximately 694 adult participants will be enrolled in the study across approximately 80 sites worldwide.
Participants will receive azirkitug as a monotherapy or in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan as an Intravenous (IV) Infusion for an estimated treatment period of up to 2 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Eligibility: 18 Years to · All · * Pre Treatment biopsy or archive tissue within 6 months without intervening treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of \<= 0 or 1 and a life expectancy of \>= 3 months.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
* Laboratory values meeting criteria outlined in the protocol
* NSCLC - Advanced or metastatic progressed on standard of care (SOC) including chemotherapy and prior anti-PD-(L)1 antibody (separately or in combination). Actionable gene alterations are eligible if failed targeted therapeutic options.
* HSNCC - Advanced/metastatic progressed on platinum and PD-1/PD-LI in recurrent or metastatic setting.
* Micro Satellite Stable Colorectal Cancer (MSS-CRC) - Progressed on Oxaliplatin, Irinotecan, a fluoropyrimidine, anti-EGFR, VEGF or VEGFR therapies, BRAFV600E or HER2, other targetable mutations targeted with locally approved therapy, TAS-102, Regorafenib and not MSI-h or MMR-deficient
* Gastric and Gastroesophageal Junction adenocarcinoma (GEA) - Advanced/metastatic progressed on at least 1 prior cytotoxic chemotherapeutic regimen and if applicable immune checkpoint inhibitor and/or HER2 therapy
* High-Grade Serous Ovarian Cancer (HGSOC) - Progressed serous epithelial ovarian, fallopian tube or primary peritoneal cancer post SOC and not eligible for surgical resection. Platinum resistant cannot have \>5 lines of prior therapy.
* Pancreatic Adenocarcinoma (PDAC) - Advanced/metastatic progressed after SOC. Includes adenosquamous carcinoma and post-Whipple.
* Triple Negative Breast Cancer (TNBC) - Progressed after 1 or 2 systemic therapy that must have included taxane and treatment naïve to immunotherapy targeting T-cell co-stimulation
NCT06492421Phase 2Recruiting
Second Affiliated Hospital of Guangzhou Medical University · The Second Affiliated Hospital of Guangzhou Medical University, Guanzhou, Guangdong
This phase II trial studies how well intra-tumor injection of double checkpoint inhibitors work when given alone and in combination with chemotherapy or/and bevacizumab in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as ipilimumab, pembrolizumab or durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Drugs used in interventional radiological chemotherapy, such as idabubicin, can directly kill the cancer cell and release tumor antigens to activate DC function in situ. Giving intra-tumor injection of checkpoints inhibitors with or without chemotherapy and/or bevecizumab may work better than in vein infusion of the drugs in treating patients with non-small cell lung cancer.
Eligibility: 18 Years to 75 Years · All · 1. Histologically or cytologically confirmed previously untreated non-small cell lung cancer. If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study.
2. Patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor.
3. All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease.
4. The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
5. Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
6. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1.
7. Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L; Hemoglobin \>= 8.0 g/dL; Platelets \>= 100 x 10\^9/L; Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin \< 3.0 mg/dL); Creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance \>= 50 mL/min.
NCT05950139Phase 1, Phase 2Recruiting
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Johns Hopkins University, Baltimore, Maryland
The purpose of this study is to evaluate the safety of a cancer peptide vaccine to prevent or delay acquired resistance in advanced ALK+ lung cancer patients currently on ALK targeted therapy.
Eligibility: 18 Years to · All · 1. Histologically or cytologically confirmed diagnosis of stage IV NSCLC (or recurrent NSCLC not a candidate for definitive multimodality therapy)
2. Documented ALK rearrangement as detected by: (1) fluorescence in situ hybridization (FISH), (2) immuno-histochemistry (IHC), (3) tissue next-generation sequencing (NGS), or (4) circulating tumor DNA (ctDNA) NGS
3. Ongoing treatment with crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib with at least stable disease ≥ 4 months
4. No known presence of the specific ALK acquired resistance alterations targeted by the study vaccine
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
6. Males or females at least 18 years old
NCT05005403Phase 1Recruiting
AbbVie · City of Hope National Medical Center /ID# 276272, Duarte, California
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. Head and Neck Squamous Cell Carcinoma (HNSCC) is a solid tumor, a disease in which cancer cells form in the tissues of the head and neck. The purpose of this study is to assess adverse events and pharmacokinetics of azirkitug as a monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan.
Bevacizumab is an approved product, while budigalimab, azirkitug, and telisotuzumab adizutecan are investigational drugs being developed for the treatment of NSCLC, HNSCC, and other solid tumors. Study doctors put the participants in groups called treatment arms. The maximum-tolerated dose (MTD)/maximum administered dose (MAD) of azirkitug will be explored. Each treatment arm receives a different dose of azirkitug in monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan. Approximately 694 adult participants will be enrolled in the study across approximately 80 sites worldwide.
Participants will receive azirkitug as a monotherapy or in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan as an Intravenous (IV) Infusion for an estimated treatment period of up to 2 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Eligibility: 18 Years to · All · * Pre Treatment biopsy or archive tissue within 6 months without intervening treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of \<= 0 or 1 and a life expectancy of \>= 3 months.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
* Laboratory values meeting criteria outlined in the protocol
* NSCLC - Advanced or metastatic progressed on standard of care (SOC) including chemotherapy and prior anti-PD-(L)1 antibody (separately or in combination). Actionable gene alterations are eligible if failed targeted therapeutic options.
* HSNCC - Advanced/metastatic progressed on platinum and PD-1/PD-LI in recurrent or metastatic setting.
* Micro Satellite Stable Colorectal Cancer (MSS-CRC) - Progressed on Oxaliplatin, Irinotecan, a fluoropyrimidine, anti-EGFR, VEGF or VEGFR therapies, BRAFV600E or HER2, other targetable mutations targeted with locally approved therapy, TAS-102, Regorafenib and not MSI-h or MMR-deficient
* Gastric and Gastroesophageal Junction adenocarcinoma (GEA) - Advanced/metastatic progressed on at least 1 prior cytotoxic chemotherapeutic regimen and if applicable immune checkpoint inhibitor and/or HER2 therapy
* High-Grade Serous Ovarian Cancer (HGSOC) - Progressed serous epithelial ovarian, fallopian tube or primary peritoneal cancer post SOC and not eligible for surgical resection. Platinum resistant cannot have \>5 lines of prior therapy.
* Pancreatic Adenocarcinoma (PDAC) - Advanced/metastatic progressed after SOC. Includes adenosquamous carcinoma and post-Whipple.
* Triple Negative Breast Cancer (TNBC) - Progressed after 1 or 2 systemic therapy that must have included taxane and treatment naïve to immunotherapy targeting T-cell co-stimulation
NCT06529822Phase 1Recruiting
Washington University School of Medicine · AdventHealth, Orlando, Florida
This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine strategy in patients with solid tumors and molecular residual disease. The hypothesis of the trial is that synthetic long peptide personalized cancer vaccines will be safe and capable of generating measurable neoantigen-specific T-cell responses enabling ctDNA clearance. The personalized cancer vaccines are composed of synthetic long peptides corresponding to prioritized cancer neoantigens and will be co-administered with poly-ICLC.
Eligibility: 18 Years to · All · Inclusion Criteria Cohort #1:
* Age ≥ 18 years.
* ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
* Histologically confirmed muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (renal pelvis and/or ureter).
* Patients with carcinomas showing mixed histologies are required to have a dominant transitional cell pattern.
* Complete surgical resection of MIBC (R0) or upper tract urothelial carcinoma (renal pelvis and/or ureter). Tumor, nodes, metastases (TNM) classification (based on the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th ed.) at pathological examination of surgical resection specimen as follows: ypT0N0M0, pT2-4N0M0, or pT0-4aN+M0.
* Patient must have fully recovered from surgical resection in the opinion of the treating MD.
* ctDNA positive result as identified by Signatera.
* Radiologic confirmation (by conventional imaging) of absence of residual disease and absence of metastasis.
* Adequate bone marrow and organ function as defined below:
* WBC ≥ 1.5 K/cumm
* Absolute neutrophil count ≥ 1.0 K/cumm
* Platelets ≥ 50 K/cumm
* Hemoglobin ≥ 8.0 g/dL
* Total bilirubin ≤ 1.5 x IULN
* AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
* Creatinine clearance \> 30 mL/min by Cockcroft-Gault
* The effects of synthetic long peptide personalized cancer vaccines and Hiltonol on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 5 months after completion of study interventions. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
* No concurrent investigational therapies outside of this protocol are allowed.
* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria Cohort #1:
* Receiving any other investigational agents, or planning to receive other investigational agents as part of neoadjuvant therapy. Patients who have received perioperative neoadjuvant chemotherapy and immunotherapy, including enfortumab vedotin plus pembrolizumab (EV+P), are allowed.
* Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
* A psychiatric illness or social situations that would limit compliance with study requirements as determined by the investigator from the medical history, physical exam, and/or medical record.
* Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. In the case of asthma or chronic obstructive pulmonary disease taking inhaled corticosteroids that does not require daily systemic corticosteroids is acceptable. Additionally, local acting steroids (topical, inhaled, or intraarticular) will be allowed. Patients on intermittent or short course steroids will be allow if the dose does not exceed 4 mg of dexamethasone (or equivalent) per day for \> 7 consecutive days. Premedication for chemotherapy does not apply to this criterion and may be administered as per SOC practice. Any patients receiving steroids should be discussed with the PI to determine if eligible.
* Known HIV-positive status.
* History of positive test for Hep
