NCT04273061Phase 2Recruiting
British Columbia Cancer Agency · BC Cancer, Vancouver, British Columbia
This study will investigate the effects of atezolizumab on select cancer types in people whose analysis of tumour DNA and RNA indicates they may be sensitive to atezolizumab. This study aims to determine if the information from the cancer genome analysis corresponds with the effects of atezolizumab on individuals and their cancer.
This is a Phase 2 study, which is undertaken after preliminary safety testing on a drug is completed, and will involve approximately 50 participants. Participants are assigned to one of 3 cohorts based on their primary tumour type: gastrointestinal (GI), sarcoma, and 'other' cancer types. Participants in all cohorts will receive the same dose of atezolizumab (1200 mg every 3 weeks). Participants continue on treatment until they no longer may benefit from the treatment or they decide to stop treatment.
Eligibility: 18 Years to · All · * Age greater than or equal to 18 years at the time of signature of informed consent.
* Participants with an incurable solid tumour who have undergone whole genome and transcriptome analysis (WGTA) as part of Personalized OncoGenomics (POG) or equivalent program.
a. Participants must have had successful sequencing of their tumour, been formally reviewed by the POG (or POG-approved) genome analysts and found to have CAPTIV-8 factors identified (including Immune, Burden, Variant (IBV) score ≥ 5), been reviewed at the Molecular Tumour Board (MTB) (or site equivalent), and allocated to a specific tumour-defined cohort (that is open for enrolment) with a final opinion documented.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Participants must have measurable disease, as defined by RECIST 1.1.
* Life expectancy of at least 12 weeks.
* Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 28 days prior to the first study treatment:
1. Absolute neutrophil count (ANC) ≥ 1500 cells/µL without granulocyte colony- stimulating factor support.
2. White blood cell (WBC) counts \> 2500/µL.
3. Lymphocyte count ≥ 500/µL.
4. Serum albumin ≥ 2.5 g/dL.
5. Platelet count ≥ 100,000/µL without transfusion (without transfusion within 2 weeks of laboratory test used to determine eligibility).
6. Hemoglobin ≥ 9.0 g/dL, participants may be transfused or receive erythropoietic treatment to meet this criterion.
7. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 × Upper Limit of Normal (ULN). This applies only to participants who are not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation must have an INR or aPTT within therapeutic limits for at least 1 week prior to enrolment.
8. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × ULN with the following exceptions: i) Participants with documented liver metastases: AST and/or ALT ≤ 5 × ULN. ii) Participants with documented liver or bone metastases: ALP ≤ 5 × ULN.
9. Serum bilirubin ≤ 1.5 × ULN. Participants with known Gilbert's syndrome who have serum bilirubin level ≤ 3 × ULN may be enrolled.
10. Serum creatinine ≤ 1.5 × ULN.
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than 1% (one percent) per year during the treatment period and for at least 5 months after the last dose of atezolizumab.
* For men: agreement to remain abstinent (refrain from heterosexual intercourse with a female partner of childbearing potential or who is pregnant) or use contraceptive measures that result in a failure rate of less than 1% (one percent) per year, and agreement to refrain from donating sperm, during the treatment period and for at least 5 months after the last dose of atezolizumab.
* Asymptomatic participants with treated or untreated CNS lesions are eligible provided that all of the following criteria are met:
1. Measurable disease, per RECIST 1.1, must be present.
2. The participant has no history of intracranial hemorrhage or spinal cord hemorrhage.
3. The participant has not undergone stereotactic radiotherapy within 7 days prior to the initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
4. The participant has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.
* Ability to give informed consent for the study procedures defined in this protocol.
NCT05019703Phase 2Recruiting
M.D. Anderson Cancer Center · Dana-Farber Cancer Institute, Boston, Massachusetts
This phase II trial studies the effect of atezolizumab and cabozantinib in treating adolescents and young adults with osteosarcoma that has come back (recurrent) or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab and cabozantinib may help to control the osteosarcoma.
Eligibility: 12 Years to · All · * Signed informed consent form
* Age \>= 12 years at time of signing informed consent form
* Ability to comply with the study protocol, in the investigator's judgment
* Histologically confirmed diagnosis of osteosarcoma
* Metastatic or unresectable locally advanced disease
* Patients must have relapsed or become refractory to conventional therapy including some combination of cisplatin, doxorubicin, methotrexate, and/or ifosfamide
* Measurable disease per RECIST version (v)1.1 (Note: Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation)
* Availability of a representative tumor specimen for exploratory biomarker research. Archival samples are permitted if the tumor samples been obtained within 6 months prior to enrollment and the patient has not received intervening therapy
* A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study enrollment. If only 10-14 slides are available, the patient may still be eligible for the study, after principal investigator confirmation has been obtained
* If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening
* Eastern Cooperative Oncology Group (ECOG) of 0, 1 or 2. Use Karnofsky \>= 50 for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age
* Body surface area (BSA) \>= 1 m\^2
* Life expectancy \>= 6 months
* Recovery to baseline or =\< grade 1 CTCAE v5 from toxicities related to any prior treatments, unless adverse events (AE\[s\]) are clinically nonsignificant and/or stable on supportive therapy
* Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L (1000/uL) without granulocyte colony-stimulating factor support (obtained within 14 days prior to initiation of study treatment)
* Lymphocyte count \>= 0.5 x 10\^9/L (500/uL) (obtained within 14 days prior to initiation of study treatment)
* Platelet count \>= 100 x 10\^9/L (100,000/uL) without transfusion (obtained within 14 days prior to initiation of study treatment)
* Hemoglobin \>= 90 g/L (9 g/dL) (obtained within 14 days prior to initiation of study treatment)
* Patients may be transfused to meet this criterion
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN) for age (obtained within 14 days prior to initiation of study treatment)
* Alkaline phosphatase (ALP) =\< 3 x upper limit of normal (ULN) for age, with the following exceptions: patients with documented bone metastases: ALP =\< 5 x ULN (obtained within 14 days prior to initiation of study treatment)
* Serum bilirubin =\< 1.5 x ULN with the following exception: patients with known Gilbert disease: serum bilirubin =\< 3 x ULN (obtained within 14 days prior to initiation of study treatment)
* Creatinine clearance \>= 50 mL/min (adults \> 18 years of age, calculated using the Cockcroft-Gault formula) or \>= 50 mL/min/1.73m\^2 (pediatrics patients age 12 - 17, calculated using the Bedside Schwartz equation) (obtained within 14 days prior to initiation of study treatment)
* Urine protein/creatinine ratio (UPCR) =\< 1 mg/mg (=\< 113.2 mg/mmol), or 24-hour (h) urine protein =\< 1 g (obtained within 14 days prior to initiation of study treatment)
* Serum albumin \>= 20 g/L (2.0 g/dL) (obtained within 14 days prior to initiation of study treatment)
* For patients not receiving therapeutic anticoagulation: international normalized ratio (INR) or activated partial thromboplastin (aPTT) =\< 1.5 x ULN (obtained within 14 days prior to initiation of study treatment)
* Negative human immunodeficiency virus (HIV) test at screening
* Negative hepatitis B surface antigen (HBsAg) test at screening
* Women of childbearing potential
NCT05542407Phase 1Recruiting
UNC Lineberger Comprehensive Cancer Center · Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina
Endometrial cancer (EC) is the fourth most common cancer in United States women, and alarmingly, the frequency and mortality from EC continues to rise, in part due to the obesity epidemic. Obese women with EC have a 6.3-fold increased risk of death from this disease, as compared to their non-obese counterparts. Patients with advanced/recurrent EC are unlikely to be cured by surgery, conventional chemotherapy (paclitaxel + carboplatin is the standard first-line treatment), radiation, or a combination of these. Thus, new treatments for EC are desperately needed as well as a better understanding of the impact of obesity on EC biology and treatment.
The purpose of this study is to test the safety of a combination of treatments, atezolizumab and ONC201, given based on body weight, to treat endometrial cancer. Using the combination of atezolizumab and ONC201, has not been approved by the Food and Drug Administration (FDA) for the treatment of endometrial cancer. This clinical trial will examine the treatment of atezolizumab + ONC201 in obese and non-obese subjects with metastatic/recurrent EC.
Eligibility: 18 Years to · Female · In order to participate in this study a subject must meet all of the eligibility criteria outlined below.
Inclusion Criteria
1. Ability to understand and willingness to sign a written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
2. Age ≥ 18 years at the time of consent.
3. ECOG Performance Status of 0, 1, or 2
4. Histologically confirmed metastatic or recurrent EC (endometrioid, carcinosarcoma, serous, clear cell, adeno-squamous and mixed histologies).
5. Subjects must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria
6. Must have radiographic disease progression after at least 1 line of systemic cytotoxic therapy for metastatic disease or with progression within 12 months of completing adjuvant chemotherapy.
7. Life expectancy of at least 3 months.
8. Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 72 hours prior to initiating study treatment.
Exclusion Criteria
1. Prior treatment with ONC201.
2. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including antiCTLA-4, and anti PD-L1 therapeutic antibodies
3. Treatment with another investigational agent or participation in another clinical trial within the last 28 days prior to initiating protocol therapy.
4. Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to initiating protocol therapy.
5. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of protocol therapy Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
6. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of protocol therapy.
7. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti TNF-agents) within 2 weeks prior to initiation
NCT07759856Phase 2Recruiting
Tianjin First Central Hospital · Tianjin First Central Hospital, Tianjin, Tianjin Municipality
This research study is designed for patients with extensive-stage small cell lung cancer (ES-SCLC) who have already received four cycles of standard chemotherapy, with at least two cycles combined with immunotherapy, and have achieved disease control (stable disease, partial response, or complete response) at their last efficacy evaluation.
In this study, participants will be randomly assigned to one of two groups:
Group A will receive standard immunotherapy plus 1 to 3 courses of allogeneic natural killer (NK) cell therapy. Each course consists of six NK cell infusions given over 28 days.
Group B will receive standard immunotherapy alone. All participants will continue treatment until their disease progresses or they experience unacceptable side effects. The immunotherapy agents used in this study are those recommended by major international and national clinical guidelines for extensive-stage SCLC, including but not limited to durvalumab, atezolizumab, serplulimab, and adebrelimab.
The purpose of this study is to evaluate whether adding NK cell therapy to standard immunotherapy can provide additional benefits for patients with extensive-stage SCLC who have responded well to initial treatment.
Eligibility: 18 Years to · All · * 1: Male or female, aged 18 years or above
2: ECOG score 0-2
3: metastatic or extensive-stage small cell lung cancer (SCLC) confirmed by histology or cytology, followed by 4 cycles of platinum-based doublet-chemotherapy with at least 2 cycles of immune checkpoint inhibitor plus chemotherapy. And stable disease (SD), partial response (PR), or complete response (CR) as assessed by imaging (RECIST1.1 criteria) after the last treatment. (The checkpoint inhibitors used were those recommended by the NCCN, ESMO, and CSCO guidelines for extensivestage SCLC, including but not limited to: Duvalumab, atezolizumab, slulizumab, adbelimumab, toripalimab, etc.)
4: After standard concurrent chemoradiotherapy, LS-SCLC could be enrolled in this study if sensitive relapse (relapse more than 6 months after the end of first-line treatment) progressed to extensive-stage (Ed) and met the inclusion criteria No.3;
5: At least 4 weeks after major surgery or trauma, and the wound must be completely healed; At least 1 week after minor surgical procedures or trauma (e.g., tissue biopsy or fine-needle aspiration);
6: Objective measurable lesions according to RECIST 1.1 criteria;
7: predicted survival time ≥1 year;
8: bone marrow function: ANC≥1.5×109/L, HB≥70 g/L (blood transfusion allowed), PLT≥80×109/L;
9: Liver function: ALT≤3×ULN, AST≤3×ULN, TBIL≤2×ULN (patients with liver metastasis ALT≤5×ULN, AST≤5×ULN, TBIL≤2×ULN) Child-Pugh score ≤7; Renal function: uric acid \<500 μmol/L, serum creatinine \<1.7 mg/dL, proteinuria ≤2+ or ≤2g/24h, glomerular filtration rate (GFR) ≥60 ml/min/1.73m2;
10: no history of autoimmune diseases or current autoimmune diseases;
11: The subjects voluntarily participated in the study, signed the informed consent form, communicated well with the investigators, and completed the study in accordance with the protocol.
NCT06830694Phase 2Recruiting
Sehhoon Park · Samsung Medical Center, Seoul, Gangnam-gu
The primary treatment option for non-small cell lung cancer (NSCLC) adenocarcinoma (ADC) with activating epidermal growth factor receptor (EGFR) mutation is EGFR tyrosine kinase inhibitor (TKI). After a certain period of treatment with EGFR TKI, acquired resistance emerges most frequently with a secondary mutation, p.T790M (36-50%), followed by MET amplification (10-19%). Interestingly, up to 3-5% of patients experience histological transformation into small cell lung cancer (SCLC).
As an underlying mechanism, ADC with a predisposed clonally inactivated Rb and p53 mutation and APOBEC mutation signature is known to be associated with SCLC transformation. The transformed SCLC harbors similar morphological and immunohistochemical (IHC) characteristics as those observed in de novo SCLC, including high expression of chromogranin and synaptophysin. However, little is known about the clinical outcomes of transformed SCLC, with limited studies arguing that their outcomes are similar to those of de novo SCLC, where the median overall survival is approximately 9 to 10 months after the transformation.
As the first line treatment of SCLC, atezolizumab or durvalumab with four cycles of conventional chemotherapy followed by maintenance therapy demonstrated prolonged overall survival (OS) and placed as the standard treatment option. However, median progression-free survival (PFS) of both study was only 5.2 months and 5.1 months, despite the objective response rate showing 60.2% and 79%. This finding suggest further development of maintenance treatment strategy to prolonged longer duration of response to the treatment.
In addition to the conventional treatment, Tarlatamab (AMG757), bispecific t-cell engager (BiTE), designed to engage DLL3 on SCLC and CD3 on T-cell has been tested in SCLC. DLL3 is expressed in more than 80% of patients with SCLC, regardless of disease stage and researched for the potential target protein for the antibody based treatment in SCLC. By targeting DLL3 using Tarlatamab, engagement of tumor antigen and CD3 lead to cytotoxic synapse formation, triggering the release of proinflammatory cytokines, perforin, and granzymes from activated T-cells, potentially resulting apoptosis. The first clinical outcome of Tarlatamab was reported from the DeLLphi-300 study, phase 1 dose exploration study, showing confirmed partial response in 23% of the heavily treated SCLC and 37% of the patients showed decrease in tumor burden. Median duration of response was 13.0 months (95% confidential interval CI: 6.2 - 14.9 months), median PFS of 3.7 months and median OS was 13.2 months. In the treatment naïve SCLC, DeLLphi-303 study, phase 1b study combining tarlatamab + PD-L1 inhibitor + carboplatin and etoposide, is ongoing to evaluate the clinical efficacy in the front line setting which include only histologically confirmed extensive disease SCLC population (NCT05361395).
Based on previous clinical and pre-clinical outcomes, showing similar disease characteristics between transformed SCLC from the adenocarcinoma who treated with EGFR TKI with de novo SCLC, this study is designed to evaluate the clinical efficacy of tarlatamab with currently standard treatment in transformed SCLC.
Eligibility: 19 Years to · All · 1. Histologically confirmed SCLC and no prior systemic treatment for SCLC
2. Patient initially diagnosed with activating EGFR mutation (L858R, Del 19) and treated with any kind of EGFR TKI.
3. Confirmed SCLC transformation right after EGFR TKI treatment failure.
4. Age ≥19 years
5. ECOG performance status of 0 to 1
6. Had at least one measurable lesion.
7. Adequate organ function
* Absolute neutrophil count ≥ 1.5 x 109/L
* Platelet count ≥ 100 x 109/L
* Hemoglobin ≥ 9 g/dL
* Estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation \> 30 mL/min/1.73 m2
* Aspartate aminotransferase and alanine aminotransferase ≤ 3 x upper limit of normal (ULN) (or ≤ 5 x ULN for subjects with liver involvement)
* Total bilirubin ≤ 1.5 x ULN (or ≤ 2 x ULN for subjects with liver metastases)
* Prothrombin time (PT)/international normalized ratio and partial thromboplastin time or activated partial thromboplastin time ≤ 1.5 x institutional ULN Note: Subjects on stable anticoagulation therapy are allowed.
8. Pulmonary function: No clinically significant pleural effusion at the timepoint of screening. Pleural effusion with no significant symptom is allowed for enrollment.
9. Cardiac function: Cardiac ejection fraction ≥ 50%
10. Female subjects must either be of non-reproductive potential
11. Female subject with reproductive potential can be enrolled with agreement to following guidance.
* subject uses contraception during treatment and through 60 days after receiving last dose of tarlatamab or for 6 months after last dose of carboplatin and/or etoposide and 5 months after last dose of atezolizumab.
12. Subject is willing and able to comply with the protocol
13. Signed written informed consent
