East Brunswick

Researchers are evaluating AV-380, an immunoglobulin G1 monoclonal antibody designed to bind human growth differentiation factor 15 GDF-15, a cytokine involved in cancer-induced cachexia. This phase 1B open-label dose escalation study aims to assess the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of AV-380 in cancer patients who have cachexia and elevated GDF-15 levels. Participants have metastatic solid tumors and are actively receiving standard of care chemotherapy. Participants receive AV-380 through intravenous infusion in ascending dose cohorts alongside their standard chemotherapy treatments. The study includes a dose escalation phase where the safety and appropriate dosage of AV-380 are evaluated. This phase allows researchers to monitor the effects of increasing doses of AV-380 over a study period of up to 4 months while patients continue their usual cancer therapies. During the study, participants will undergo assessments including monitoring for adverse events, toxicity, and laboratory abnormalities from enrollment until about 60 days after the last dose. Pharmacokinetic measures such as maximum concentration Cmax, time to maximum concentration Tmax, and area under the curve AUC will also be evaluated. The total involvement includes regular evaluations to track safety, drug behavior in the body, and immune responses to AV-380.

Researchers are studying MEN2312, a lysine acetyltransferase 6 KAT6 inhibitor, in adults with advanced breast cancer that is not curable. This first-in-human, phase 1 study evaluates MEN2312 alone and in combination with elacestrant to understand its safety and determine the best dose. Participants have specific genetic alterations in their tumors and have received prior endocrine therapy and cyclin-dependent kinase 4 and 6 inhibitor treatment. Participants will be randomly assigned to receive either MEN2312 by itself or MEN2312 combined with elacestrant, both given as oral tablets. The study follows a sequential design and aims to identify dose-limiting toxicities and recommend the phase 2 dose over several months of treatment. This includes monitoring drug levels in the body and how the body processes the medications. During the study, participants will have regular assessments to monitor side effects, tumor response, and overall health. These include evaluating the number of dose-limiting toxicities within the first 28 days and tracking response rates, progression-free survival, and overall survival for up to nine months after treatment ends. Researchers will also measure drug concentration and excretion to better understand the treatment effects and safety over time.

Researchers are evaluating the efficacy and safety of volrustomig compared to observation in participants with unresected locally advanced head and neck squamous cell carcinoma LA-HNSCC who have not progressed after receiving definitive concurrent chemoradiotherapy cCRT. This phase III, randomized, open-label global study aims to assess whether volrustomig can improve outcomes in this patient population. Participants are randomly assigned to one of two groups those who receive volrustomig as sequential therapy, and those who undergo observation without additional treatment. The study compares these two approaches following prior curative concurrent chemoradiotherapy. The trial includes long-term follow-up to monitor patient outcomes. During the study, participants will be regularly assessed for progression-free survival, overall survival, physical functioning, and quality of life. Researchers will also monitor for the presence of anti-drug antibodies and adverse events related to volrustomig. Follow-up evaluations may continue for up to approximately eight years to fully understand the treatment impact and safety profile.

Researchers are evaluating the efficacy and safety of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced Stage III, unresectable non-small cell lung cancer NSCLC whose disease has not progressed after definitive platinum-based concurrent chemoradiotherapy cCRT. This Phase III, randomized, double-blind, placebo-controlled, international study aims to provide new insights into treatment options for this patient population. Participants will receive either durvalumab and domvanalimab or durvalumab plus placebo as intravenous infusions every four weeks, beginning on Day 1 and continuing for up to 12 months. The study includes two groups one receiving the combination of durvalumab and domvanalimab, and the other receiving durvalumab with a placebo. Both treatments are given through infusion to assess their effects on disease progression and safety. During the trial, participants will undergo regular assessments including monitoring progression-free survival for up to 8 years after randomization. Other measures include overall survival, response rates, duration of response, and various time-to-event outcomes related to disease progression and symptom deterioration. Researchers will also evaluate drug concentrations and immune responses approximately 12 weeks after the last dose. Participants can expect scheduled visits for infusions and evaluations as part of this long-term study.

Researchers are evaluating the safety, tolerability, pharmacokinetics PK, pharmacodynamics PD, and preliminary anti-tumor activity of increasing doses of EPI-326 in patients with locally advanced or metastatic head and neck squamous cell carcinoma HNSCC and those with EGFR-mutant locally advanced or metastatic non-small cell lung cancer NSCLC. This first-in-human, phase 1 multicenter, open-label study aims to determine appropriate dosing and assess initial effects of EPI-326 in these patients. EPI-326 is a tissue-selective bispecific antibody targeting EGFR-driven cancers and is administered by intravenous infusion in the clinic. Patients will receive escalating doses of EPI-326 as a single agent until they experience disease progression, unacceptable side effects, choose to withdraw, or the study ends. This study includes a dose escalation period to identify the recommended dose and schedule for administration. Participants will be monitored for safety and tolerability, with assessments including blood tests to measure drug concentration over time, clearance, and distribution. Researchers will also evaluate tumor response and duration of response over a period of up to three years. The study involves continuous treatment and follow-up visits to observe effects and manage any adverse events during the trial period.

Researchers are conducting a Phase 1a1b open-label study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of PLN-101095 combined with pembrolizumab in adults with advanced or metastatic solid tumors. Participants must have tumors for which pembrolizumab is indicated and must show disease progression or relapse after at least three months of pembrolizumab treatment. The study includes consecutive dose-escalation and dose-expansion cohorts to explore different dosing levels and tumor types. The study has two main parts Part 1 uses a Bayesian optimal interval design for dose escalation with accelerated titration to test increasing doses of PLN-101095 combined with pembrolizumab, while Part 2 uses Simons two-stage design for dose expansion. Doses of PLN-101095 range from 250 mg twice daily up to 2000 mg twice daily or 1000 mg three times daily, given in combination with pembrolizumab administered intravenously every three weeks. Participants in expansion cohorts include those with non-small cell lung cancer, clear cell renal cell carcinoma, or tumor mutational burden-high solid tumors, receiving PLN-101095 as monotherapy or combined with pembrolizumab. Participants will be monitored for safety and tolerability from first dose through 16 weeks after treatment ends, and anti-tumor activity will be measured from first dose until disease progression or death. Pharmacokinetics of PLN-101095 will be assessed at specified time points. The study evaluates participants measurable lesions and organ function, with follow-up assessments for adverse events and treatment response. The total duration varies depending on treatment response and tolerability, with ongoing monitoring throughout the study period.

Researchers are evaluating zanidatamab combined with chemotherapy for treating people with HER2-positive, early-stage breast cancer. This phase 2 study aims to assess the safety and effectiveness of this combination compared to standard treatments in participants with newly diagnosed stage II or III invasive breast carcinoma. Participants are randomly assigned to one of three treatment groups zanidatamab with paclitaxel, zanidatamab with docetaxel and carboplatin, or trastuzumab and pertuzumab with docetaxel and carboplatin. All study drugs are administered intravenously. After neoadjuvant therapy, participants will undergo either mastectomy or breast conserving surgery as decided by their physician. During the study, participants will have their response to treatment assessed through measurements such as pathologic complete response and residual cancer burden classification up to 8 months. Safety is monitored by tracking treatment-related adverse events up to 23 months. Other assessments include survival outcomes up to 46 months and serum concentrations of zanidatamab. The study participation may last several years to capture these outcomes.

Researchers are evaluating the safety and effectiveness of VS-7375, an oral KRAS G12D inhibitor, alone and in combination with cetuximab or panitumumab, and cetuximab plus mFOLFOX chemotherapy in patients with metastatic KRAS G12D-mutated colorectal cancer. This phase 2 study focuses on patients with advanced colorectal cancer who have specific genetic mutations and aims to explore treatments for different lines of therapy. Participants will be randomly assigned in a 21 ratio to receive either VS-7375 alone or combined with cetuximab or panitumumab, or VS-7375 combined with cetuximab and mFOLFOX chemotherapy. Treatments include oral administration of VS-7375 daily and intravenous infusions of cetuximab, panitumumab, and mFOLFOX. The study includes groups for patients receiving second-line or later therapy and treatment-nave patients or those with limited prior treatment. During the study, participants will undergo evaluations including imaging to measure tumor response, pharmacokinetic and pharmacodynamic blood tests, and quality of life questionnaires. Safety and tolerability of treatments will be closely monitored over six months, with longer-term assessments up to two years for some outcomes. The primary measure is confirmed objective response rate by independent review using RECIST criteria. The total participation duration varies, with ongoing follow-up to assess treatment impact and safety.

Researchers are evaluating the safety and effectiveness of VS-7375, taken alone or combined with cetuximab, in patients with metastatic Non-Small Cell Lung Cancer NSCLC that has the KRAS G12D mutation. This Phase 2 study focuses on individuals whose cancer has progressed after prior chemotherapy and immunotherapy treatments. Participants receive oral VS-7375 in different dosing schedules depending on their prior treatment lines and presence of brain metastases. The study includes groups receiving the drug as second or third line therapy, and a separate group for those with brain metastases treated between second and fourth line. Treatment is given daily by mouth, and participants may cross over between groups during the trial. During the study, participants undergo regular assessments including imaging for tumor response using RECIST criteria, blood tests to monitor drug levels and tumor markers, and quality of life questionnaires. Safety and tolerability are closely monitored over six months, with additional follow-up up to two years to measure overall response, progression, and health status. The total participation duration varies based on treatment response and trial phase completion.

Researchers are evaluating the safety and effectiveness of the oral drug VS-7375 alone and combined with the drug cetuximab in patients who have metastatic pancreatic cancer with a specific KRAS G12D mutation. This Phase 2 clinical trial focuses on understanding how well these treatments work and their safety profiles in this particular group of patients. Participants may receive VS-7375 by mouth either alone or with cetuximab given as a subcutaneous infusion. The study includes different groups where participants receive either VS-7375 alone, VS-7375 plus cetuximab as a second-line treatment, or VS-7375 plus cetuximab as a first-line treatment. The trial involves random assignment to these groups and includes a crossover design. During the study, participants will be monitored for their tumor response using imaging reviewed by an independent central team according to RECIST criteria. Safety and tolerability of the treatments will also be assessed over six months. Additional evaluations include measuring drug levels in the blood, tumor markers, quality of life through questionnaires, and timing until the next therapy. The trial is expected to continue until December 2028.