Lafayette

Researchers are evaluating if combining the medicines calderasib and subcutaneous pembrolizumab can more effectively treat people with non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The study aims to find out whether patients receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a Phase 3 clinical trial focusing on first-line treatment for advanced or metastatic nonsquamous NSCLC. Participants are assigned to one of two groups. One group receives subcutaneous pembrolizumab plus berahyaluronidase alfa every 6 weeks for up to 18 cycles about 2 years along with oral calderasib until treatment discontinuation criteria are met. The other group receives the same pembrolizumab and berahyaluronidase alfa regimen plus chemotherapy with pemetrexed and either carboplatin or cisplatin infusions during the early cycles. Treatment continues based on individual response and tolerability. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess progression-free survival, overall survival, response rates, and quality of life using questionnaires and symptom scores over several years. Safety will be monitored through adverse event reporting. The trial lasts up to about 7 years with ongoing evaluation of health outcomes and side effects to understand the impact of these treatment combinations.

Researchers are evaluating HB0036, a drug being studied for patients with advanced solid tumors, including non-small cell lung cancer NSCLC. This Phase III, open-label, multicenter trial aims to assess the safety, pharmacokinetics, pharmacodynamics, and effectiveness of HB0036. The study includes patients with locally advanced, recurrent, or metastatic solid tumors who have not responded to standard treatments. A Safety Review Committee will monitor safety data throughout the trial. Participants receive HB0036 through intravenous infusion every three weeks. The study is divided into two phases Phase I focuses on safety and tolerability, while Phase II evaluates safety and efficacy at the recommended Phase II dose in specific tumor groups, including NSCLC and other solid tumors. The study may adjust dosing schedules or include additional tumor types based on safety findings. During the study, participants undergo evaluations including tumor assessments by CT or MRI scans, blood tests to monitor organ function, and performance status checks. Researchers will measure safety and tolerability for up to 12 months and determine the maximum tolerated dose for up to 24 months. Pharmacokinetic parameters such as drug exposure and concentration will also be monitored. Total participation duration varies by patient condition and response.

Researchers are evaluating whether adding sacituzumab tirumotecan to pembrolizumab after surgery improves treatment outcomes for adults with resectable non-small cell lung cancer NSCLC who do not achieve a complete response after initial therapy. This Phase 3 trial compares the combination of sacituzumab tirumotecan plus pembrolizumab against pembrolizumab alone, focusing on disease-free survival assessed by a blinded independent central review. The study is sponsored by Merck Sharp & Dohme LLC and targets participants with specific stages of NSCLC who have undergone neoadjuvant therapy and surgery but still have residual disease. Participants first receive neoadjuvant therapy consisting of pembrolizumab combined with double-platinum chemotherapy tailored to the tumor type for up to 12 weeks before surgery. After surgery, those not achieving pathological complete response are assigned to either receive sacituzumab tirumotecan infusions every two weeks for up to 24 weeks alongside pembrolizumab monotherapy every six weeks for approximately 42 weeks, or pembrolizumab monotherapy alone on the same schedule. Rescue medications to manage infusion reactions may be given as needed during the study. Throughout the trial, participants undergo assessments including radiological scans, tumor tissue analysis for markers like PD-L1 and TROP2, and monitoring for adverse events and quality of life changes. Key outcomes include disease-free survival, overall survival, distant metastasis-free survival, and lung cancer-specific survival, with evaluations continuing for up to nearly 10 years. Safety and tolerability are closely monitored, and questionnaires assess physical functioning, symptoms like cough and chest pain, and overall health status during and after treatment.

Researchers are evaluating the safety, tolerability, and pharmacokinetics of INV-1120 alone and in combination with pembrolizumab in adult patients with advanced solid tumors. This phase 1, open-label, dose-escalation study aims to determine the maximum tolerated dose MTD, recommended phase 2 dose RP2D, and dose-limiting toxicities DLT of INV-1120 as a single agent or combined with pembrolizumab. The trial includes patients whose tumors have progressed after standard therapies or have no standard treatment options. In Phase 1a, approximately 36 patients will receive escalating oral doses of INV-1120 once daily until unacceptable toxicity or disease progression occurs. Up to 9 additional patients may be enrolled to confirm safety at the MTDRP2D. In Phase 1b, around 36-42 patients will receive escalating and de-escalating doses of oral INV-1120 combined with pembrolizumab, administered as 200 mg intravenously on Day 1 of each 3-week cycle, until toxicity or disease progression. Safety and tolerability of the combination will be confirmed in an expanded group of 12-15 patients. Participants will undergo safety evaluations during the first treatment cycle, including assessment of dose-limiting toxicities over 21 to 28 days depending on the phase. Researchers will monitor tumor response using imaging scans and assess pharmacokinetics through blood tests. Safety will be tracked using standard criteria for adverse events. The study period for primary outcome assessment is up to 12 months, during which patients will be closely observed for response, side effects, and drug levels to inform future dosing and treatment strategies.

Researchers are studying how certain factors like age, gender, other medical conditions, and the type of immunotherapy affect whether patients with malignant solid tumors develop mild or serious side effects from immune checkpoint inhibitor treatments. This observational study aims to develop and validate a model that predicts severe immune-related side effects during the first year of immunotherapy, while also assessing quality of life and adverse events over 12 months. The study is sponsored by the SWOG Cancer Research Network and includes translational medicine goals such as evaluating cytokine levels as predictors and establishing a tissue and blood sample repository. Participants will provide a tissue sample at the start of their routine cancer treatment and complete questionnaires at multiple time points at treatment start, and weeks 4, 12, 24, and 52. They may also provide optional blood samples during the study. This design allows researchers to monitor immune-related side effects and patient-reported outcomes over time. During the study, participants will complete various questionnaires to report their quality of life, cognitive function, and side effects. Blood and tissue samples will be analyzed to explore predictive markers of toxicity. Researchers will track the occurrence of severe immune-related side effects over 52 weeks and assess changes in patient-reported outcomes. The study includes ongoing monitoring and data collection, with participation lasting approximately one year from treatment start.

Researchers are comparing the rates of surgical and minimally invasive interventions, as well as any harms, in Medicare beneficiaries treated with the MILD procedure versus those treated with interspinous process decompression IPD for lumbar spinal stenosis with neurogenic claudication. This observational study uses Medicare claims data to follow patients for 24 months after their initial procedure starting from January 1, 2017. The purpose is to evaluate outcomes between these two types of procedures without requiring prior patient enrollment or consent. The study includes two groups patients who received MILD, which is a percutaneous image-guided lumbar decompression performed under fluoroscopic guidance through a dorsal approach to the spine, and patients who received IPD, a different device-based decompression procedure. Data on reoperations and complications will be collected for both groups over a 24-month follow-up period using Medicare claims. Enrollment continues until the sponsor decides to stop. Participants involvement is passive as the study uses existing Medicare claims data. Researchers will monitor rates of harms related to the initial procedure and subsequent surgical or minimally invasive interventions over two years. No direct patient visits or interventions are conducted, and the study is exempt from institutional review board oversight. The total study duration extends to December 2026, covering cases treated since early 2017.

Researchers are evaluating patients with metastatic HER-2-positive breast cancer who are receiving trastuzumab-based therapy and are at risk of heart problems. The study includes two groups one large observational group taking beta blockers, ACE inhibitors, or ARBs alongside trastuzumab, and a smaller randomized group comparing the effects of carvedilol versus no treatment. The aim is to understand the occurrence of heart issues and whether carvedilol might help prevent cardiac side effects from chemotherapy. Participants are assigned to one of three arms based on their current medications. Patients not on beta blockers, ARBs, or ACE inhibitors are randomized to either receive carvedilol orally twice daily or no study intervention. Those already taking these heart medications enter an observational arm without additional treatment. Treatment and observation continue for up to 108 weeks unless disease progression or unacceptable side effects occur. Throughout the study, participants undergo heart function monitoring with echocardiograms every 12 weeks and provide blood samples for biomarker analysis. Researchers track the time to the first sign of heart dysfunction and any cardiac events, as well as adherence to medication and side effects. The study also collects data to develop models predicting heart risk and banks samples for future research. Participant involvement may last over two years with regular assessments to monitor safety and heart health.

Researchers are evaluating how well serum tumor marker directed disease monitoring STMDDM works compared to usual care in patients with hormone receptor positive, HER2-negative metastatic breast cancer. This trial aims to see if monitoring with serum tumor markers can provide similar overall survival outcomes to the standard approach, which involves regular imaging scans. The study also looks at healthcare costs, patient anxiety, and quality of life related to these monitoring methods. Participants are randomly assigned to one of two groups. In the usual care group, patients receive imaging studies at least every 12 weeks and may have serum tumor marker tests as determined by their doctor. In the STMDDM group, patients have blood tests for specific tumor markers every 4 to 8 weeks, and imaging scans are only done if these markers indicate a possible progression of disease. Both groups continue their monitoring for up to 312 weeks unless the disease progresses. During the study, participants undergo regular assessments including blood tests for tumor markers, imaging scans as needed, and questionnaires about anxiety and quality of life. Researchers track overall survival for up to 312 weeks and compare healthcare costs and patient-reported outcomes for up to 48 to 102 weeks. The study also collects data on how often and by what methods disease monitoring is performed, along with patient and physician preferences related to monitoring.

Researchers are evaluating MBRC-101, an anti-EphA5 monomethyl auristatin E MMAE antibody drug conjugate, in patients with advanced metastatic solid tumors that have not responded to standard treatments. This first-in-human, open-label study includes Phase 1, Phase 1b, and Phase 2 phases to identify optimal dosing, assess safety, and evaluate preliminary clinical activity and efficacy in specific tumor types. The study is sponsored by MBrace Therapeutics and focuses on patients with no known beneficial standard care options. The study begins with Phase 1 dose escalation to find the maximum tolerated dose MTD and optimal biologically relevant doses OBRD of MBRC-101 in about 30 patients. Phase 1b involves dose expansion with approximately 60 patients across three cohorts with specific tumor types. After determining the recommended Phase 2 dose RP2D in Phase 1b, Phase 2 will enroll around 30 patients with a specific tumor type identified earlier to evaluate anti-tumor activity and safety. Safety is closely monitored throughout by a Safety Review Committee. Participants will undergo assessments including PET-CT, CT, and MRI scans evaluated by RECIST v1.1 criteria to measure response rates and disease control. Researchers will monitor treatment-emergent adverse events and dose-limiting toxicities over up to 24 months. Pharmacokinetic profiles and antibody incidence will be characterized. The study involves multiple treatment cycles with ongoing evaluations of overall response, progression-free survival, and overall survival to understand MBRC-101s effects and safety in this patient population.

Researchers are evaluating whether the combination of sacituzumab govitecan-hziy SG and pembrolizumab given after surgery is effective and safe compared to the treatment of physicians choice TPC in adults with triple negative breast cancer that remains after surgery and pre-surgical therapy. This phase 3 trial focuses on participants who have residual invasive disease following neoadjuvant therapy and surgery. The study aims to better understand outcomes for this condition where cancer persists despite earlier treatments. Participants are randomly assigned to one of two groups. One group receives SG intravenously at 10 mgkg on Days 1 and 8 of 21-day cycles along with pembrolizumab 200 mg intravenously on Day 1, repeated for up to 8 cycles. The other group receives physicians choice treatment pembrolizumab alone or pembrolizumab combined with oral capecitabine, also given over 8 cycles. Treatment continues until 8 cycles are completed, disease recurrence, unacceptable side effects, or other specified reasons. During the study, participants are monitored for invasive disease-free survival up to 60 months, along with overall survival, distant disease-free survival, recurrence-free survival, and quality of life measures. Safety is assessed through tracking treatment-related adverse events and laboratory tests for up to 38 months plus 30 days. This long-term follow-up helps evaluate the impact of the treatments on disease outcomes and participant well-being.