NSCLC, Non-Small Cell Lung Cancer, Lung Cancer, Prostate Cancer, Thymic Epithelial Tumors, TETs, Thymic Carcinomas, Thymomas, Metastatic Castrate-resistant Prostate Cancer, mCRPC
Conditions
Keywords
Antibody, T-cell receptors, programmed cell death protein 1 (PD-1)
Brief summary
Background: Immunotherapy is a type of treatment that works by making the body s own immune system stronger. These treatments are used for cancers such as non small cell lung cancer (NSCLC); thymic carcinoma (TC); or metastatic castrate-resistant prostate cancer (mCRPC). But these cancers may still come back after treatment. Objective: To test a new immunotherapy drug (STAR0602), alone or combined with an approved drug (nivolumab), in people with NSCLC, mCRPC, or TC. Eligibility: People aged 18 years or older with NSCLC, mCRPC, or TC that did not respond to treatment or returned after treatment. Design: Participants will be screened. They will have blood and urine tests. They will have imaging scans and a test of their heart function. STAR0602 and nivolumab are given through a needle inserted into a vein (infusion). Participants will be treated in 28-day cycles. They will receive infusions of 1 or both drugs on the first and 15th day of each cycle. They will remain in the hospital for up to 5 days after their first 2 infusions of STAR0602. Imaging scans, blood tests, and other tests may be repeated during study visits. Participants may opt to have tissue samples (biopsies) taken from their tumors. Some blood and tissue samples may be used for genetic tests. Participants may continue getting STAR0602 for up to 2 years and nivolumab for up to 6 months. Participants will have an end-of-study visit within 1 month, and follow-up phone calls 1 month and 3 months, after they stop the study drug. Long-term follow-up calls and visits will continue every 3 to 6 months for up to 5 years.
Detailed description
Background: * Non-small cell lung cancer (NSCLC), which encompasses three main histological subtypes (adenocarcinoma, squamous cell, large cell), accounts for approximately 85% of lung cancers. * Immunotherapy is utilized in the neoadjuvant and adjuvant settings for resectable NSCLC and is an integral component of frontline therapy for patients with metastatic disease. However, less than 50% of patients with advanced-stage NSCLC respond to immune checkpoint inhibitors (ICIs). * Among men in the United States, prostate cancer (PC) is the second leading cause of cancer-related mortality. Though androgen deprivation therapy (ADT) is highly effective for advanced-stage PC, most patients will progress to castration resistance. * Prostate cancer is considered an immunologically "cold" tumor, limiting the effectiveness of immunotherapy alone. However, combining immune checkpoint inhibitors with other systemic treatments - such as androgen receptor-targeting agents, additional ICIs, or targeted therapies like olaparib -may enhance therapeutic efficacy in patients with advanced or aggressive disease. * Thymic epithelial tumors (TETs) are rare cancers with an annual incidence of 0.48 (for thymic carcinomas \[TC\]) to 2.2 (for thymomas) per million individuals in the United States. These tumors are characterized by a low tumor mutation burden, a lack of actionable genomic changes, and defects in immune tolerance. * A subset of patients with TETs treated with ICIs derive durable clinical benefit, and longer survival is observed in patients achieving an objective response as compared to those with stable disease (SD). * STAR0602 is a fully human, bifunctional antibody that binds to Vbeta6/Vbeta10 T-cell receptors (TCRs) promoting the activation and expansion of predominantly CD8+ Vbeta6/Vbeta10 T cells with augmented cytotoxic function and a central memory-like T cell (TCM) phenotype and upregulation of IL-2 receptor (IL-2R) alpha chain. * Nivolumab is a monoclonal antibody against PD-1 which has shown an acceptable tolerability profile and antitumor activity in multiple solid tumors. * STAR0602 may offer a safe and effective therapeutic option for patients who progress after treatment with checkpoint inhibitors (CPIs). Further, preclinical data suggest that objective response and possibly overall survival may be enhanced through use of combination therapy whereby STAR0602 is administered before an anti- programmed cell death protein 1 (PD-1) therapy, such as nivolumab. Objectives: * Phase Ib: To determine the safety of STAR0602 monotherapy in participants with thymic carcinoma (TC), and safety of STAR0602 in combination with nivolumab in participants with non-small cell lung cancer (NSCLC) with or without targetable genomic alterations or metastatic castrate-resistant prostate cancer (mCRPC) * Phase II: To determine the clinical efficacy of STAR0602 alone in participants with TC measured by progression-free survival (PFS) Eligibility: * Age \>=18 years * Histologically or cytologically confirmed diagnosis of NSCLC, mCRPC, or TC * Participants should have at least one measurable lesion. * Eastern Cooperative Oncology Group (ECOG) performance status \<=2 Design: * This is an open label, nonrandomized Phase Ib/II study assessing the safety and clinical activity of STAR0602 monotherapy in participants with TC, and STAR0602 with nivolumab in participants with NSCLC or mCRPC. * Participants with TC will receive STAR0602 by intravenous (IV) infusion on Day 1 and 15 of every 28-day cycle. * Participants with NSCLC or mCRPC will receive STAR0602 and nivolumab by intravenous (IV) infusion on Day 1 and 15 of every 28-day cycle with the exception of Cycle 1 where nivolumab will be only administered on Day 15. * Participants will receive STAR0602 for up to 24 months (24 cycles) and nivolumab for up to 6 months (6 cycles), or until disease progression or development of intolerable adverse events, whichever occurs first. * Up to 52 evaluable participants will be enrolled.
Interventions
DRUGSTAR0602
STAR0602 is given intravenously (IV) on day 1 and 15 of every 28-day cycle for up to 24 months (24 cycles)
DRUGNivolumab
Nivolumab is given intravenously (IV) on day 1 and 15 of every 28-day cycle (with the exception of cycle 1 where nivolumab will only be administered on day 15) for up to 6 months (6 cycles)
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: * Participants must have histologically or cytologically confirmed NSCLC, mCRPC, or TC (by outside pathology report or via the NCI Laboratory of Pathology \[LP\]) that is unresectable, locally-advanced, or metastatic, and for which standard curative therapies do not exist or are no longer effective. Progressive disease must be documented prior to study entry. * The following tumor types and prior treatments will be included: * NSCLC: Participants must have received at least one prior approved line of standard therapy. Receipt of prior immune checkpoint inhibitors (ICI) is required unless the participant has a known targetable oncogenic abnormality (e.g., targetable EGFR mutations, KRAS G12C, ALK rearrangement, ROS1 rearrangement, BRAF V600E mutation, NTRK 1/2/3 gene fusion, METex14 skipping mutation, RET rearrangement, ERBB2 \[HER2\], NRG1 gene fusion) that has been treated with appropriate targeted therapy. Prior ICI therapy is not required for participants with NSCLC harboring a targetable oncogenic abnormality. * mCRPC: Participants must have received at least one prior line of treatment with enzalutamide and/or abiraterone with the exception of participants who were treated with docetaxel and androgen deprivation therapy (ADT) for mCRPC and progressed on docetaxel treatment or who progressed within one month of the last docetaxel dose. Participants must agree to continue ADT with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy. * TC: Participants should have received at least one prior line of standard therapy such as platinum-based chemotherapy. For participants who refuse cytotoxic chemotherapy, a rationale for refusal to receive standard first-line therapy will be captured in the case report form and the medical record. Receipt of prior ICI is permitted. * Presence of \>= 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) * Age \>=18 years * Eastern Cooperative Oncology Group (ECOG) performance status \<= 2 * Adequate organ and marrow function as defined below: * Absolute Neutrophil Count (ANC) \>= 1500/mcL * Platelets \>= 75,000/mcL * Hemoglobin (Hgb) \>= 8.5 g/dL * Total bilirubin \<= 1.5 X institutional upper limit of normal (iULN), except participants with Gilbert s syndrome, who may be enrolled if the conjugated bilirubin is within normal limits. * Aspartate aminotransferase (AST) \<= 3 X iULN -OR- \<= 5 X ULN for participants with documented metastatic liver disease * Alanine aminotransferase (ALT) \<= 3 X iULN -OR- \<= 5 X ULN for participants with documented metastatic liver disease * Creatinine clearance \>= 50 mL/min calculated using estimated glomerular filtration rate (eGFR) * Castrate testosterone level (\<50 ng/dl or 1.7 nmol /L) (in participants with mCRPC only) * Participants with symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic for \>= 14 days, are not receiving concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids \>10 mg prednisone/day or equivalent), and do not have concurrent leptomeningeal disease or cord compression. Participants with incidentally discovered, asymptomatic CNS metastases that do not require CNS-directed therapy in the judgment of the investigator, are eligible for the trial. * Human immunodeficiency virus (HIV)-infected participants must have CD4+ T cell (CD4+) counts \>= 350 cells/mcL and HIV viral load (VL) \< 400 copies/mL. * Women of child-bearing potential (WOCBP) must agree to use an effective form of contraception (barrier, hormonal, intrauterine device, surgical sterilization, abstinence) while taking study drugs and for 90 days after the last dose of STAR0602 or 5 months after the last dose of nivolumab whichever comes later. A participant may request a male partner to use an effective form of contraception to fulfill this requirement. Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) while taking study drugs and for 90 days after the last dose of STAR0602 or 5 months after the last dose of nivolumab whichever comes later. A participant may request a female partner to use an effective form of contraception to fulfill this requirement. Men should refrain from fathering a child or donating sperm during the same period. * Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 90 days after the last dose of STAR0602 or 5 months after the last dose of nivolumab whichever comes later. * Participants must be able to understand and willing to sign a written informed consent document.
Exclusion criteria
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to STAR0602, or other agents used in study. * Detectable acetylcholine receptor autoantibodies or anti-striational antibodies due to the risk of immune myositis (for participants with TC only). * Persisting toxicity related to prior therapy (NCI CTCAE Grade \> 1 or baseline) with the exception of, alopecia, sensory neuropathy Grade \<= 2 and hearing loss Grade \<= 2. Note: Prior ICI-related endocrine abnormalities are permitted regardless of grade if receiving replacement therapy. * Participants with history of prior ICI-related Grade \> 3 pneumonitis, pericarditis, myocarditis, colitis or any neurological or neuromuscular toxicities. * Treatment with \>10 mg per day of prednisone (or equivalent) or other immunesuppressive drugs within 7 days prior to the initiation of study drug (or 5 half-lives of the drug, whichever is shorter). Exceptions will be made for participants who have had an allergic reaction to iodinated contrast media or those receiving hormonal replacement therapy for previously diagnosed endocrinopathies. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed. * Participants receiving any other investigational agents. * Prior therapy within the following timeframe with: * Cytotoxic chemotherapy, ICI, small molecule inhibitors, radiation, interventional radiology procedure, or similar investigational therapies within 2 weeks prior to the initiation of study drug(s); * Monoclonal antibodies (except ICIs), antibody-drug conjugates, radioimmunoconjugates, or similar investigational therapies within 6 weeks prior to the initiation of study drug. Note: Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes, hormone replacement therapy) or use of gonadotropin-releasing hormone analogue/antagonist for androgen deprivation in mCRPC is acceptable. Bisphosphonates or denosumab are permitted for supportive care of bone metastases. Palliative radiotherapy is permitted to non-target lesions. * Known autoimmune disease except for: * Vitiligo * Psoriasis, atopic dermatitis, or other autoimmune skin condition not requiring systemic treatment * Endocrinopathies managed by endocrine replacement therapy * Alopecia * Arthritis managed without systemic therapy beyond oral nonsteroidal anti-inflammatory drugs * TC-associated paraneoplastic syndromes that do not require systemic immunosuppressive therapy * Active second malignancy within the past 12 months, except for basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of the breast, papillary or follicular thyroid carcinoma, non-muscle invasive bladder cancer and any malignancy that has been definitively/curatively treated without evidence of relapse. * Participants must not have received major surgeries within 4 weeks prior to the first study drug administration. * Active infection requiring systemic therapy or significant acute or chronic infections including, among others, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (positive HBV surface antigen \[HBsAg\] or HCV RNA if anti-HCV antibody test is positive) * Vaccination with any live virus vaccine within 4 weeks before the initiation of study drug administration. * Positive serum or urine beta-human chorionic gonadotropin (beta-hCG) test at screening (WOCBP only) * Severe uncontrolled intercurrent illness as evaluated by history, physical exam, electrocardiogram (EKG) and labs that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib: Determine the safety of STAR0602 monotherapy in participants with TC, and safety of STAR0602 in combination with nivolumab in participants with NSCLC with or without targetable genomic alterations or mCRPC | Start of therapy through 90 day post last dose safety visit. | The number of adverse events by grade and type will be reported in each cohort along with a 95% confidence interval. Dose-limiting toxicities (DLTs) will also be collected and reported by type, grade, and frequency. |
| Phase II: Determine the clinical efficacy of STAR0602 alone in participants with TC measured by progression free survival (PFS) | Cycle 3 Day 1, Cycle 4 Day 1, then every 8 weeks for the first year and every 12 weeks thereafter until disease progression, start of another systemic therapy, or 5 years after completion of study treatment. | Proportion of participants attaining progression free survival (PFS) will be evaluated and reported along with a 95% confidence interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate safety of STAR0602 alone during Phase II | Start of therapy through 90 day post last dose safety visit. | The number of adverse events by grade and type will be reported in each cohort along with a 95% confidence interval. Dose-limiting toxicities (DLTs) will also be collected and reported by type, grade, and frequency. |
| To evaluate the efficacy of STAR0602 + nivolumab as defined by progression free survival (PFS) in participants with NSCLC or mCRPC | Cycle 3 Day 1, Cycle 4 Day 1, then every 8 weeks for the first year and every 12 weeks thereafter until disease progression, start of another systemic therapy, or 5 years after completion of study treatment. | Proportion of participants attaining progression free survival (PFS) will be evaluated and reported along with a 95% confidence interval. |
| Determine the overall response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS) of STAR0602 + nivolumab in participants with NSCLC or mCRPC | For ORR, DCR, DOR: C3D1, C4D1, then every 8 weeks for 1 year and every 12 weeks thereafter for up to 5 years after end of treatment. For OS: Start of therapy through 5 years after completion of treatment. | Overall response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS) will be calculated as simple proportions from the on-study date and reported along with a 95% confidence interval for the median time if appropriate, or for selected time points such as at 1 or 2 years. |
| Determine the overall response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS) of STAR0602 in participants with TC | For ORR, DCR, DOR: C3D1, C4D1, then every 8 weeks for 1 year and every 12 weeks thereafter for up to 5 years after end of treatment. For OS: Start of therapy through 5 years after completion of treatment. | Overall response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS) will be calculated as simple proportions from the on-study date and reported along with a 95% confidence interval for the median time if appropriate, or for selected time points such as at 1 or 2 years. |
Countries
United States
Contacts
CONTACTChristine A Feierabend
CONTACTArun Rajan, M.D.
PRINCIPAL_INVESTIGATORArun Rajan, M.D.
National Cancer Institute (NCI)
Outcome results
None listed