A Phase 1/2a Multicenter Open-Label First in Human Study to Assess the Safety Tolerability Pharmacokinetics and Preliminary Antitumor Activity of DB-1303 in Patients with Advanced/Metastatic Solid Tumors
This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1303 in subjects with advanced solid tumors that express HER2.
A Phase 1/2a Open-label Study of VS-7375 a KRAS G12D (ON/OFF) Inhibitor as Monotherapy and in Combination in Patients with Advanced KRAS G12D-Mutant Solid Tumors
VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D inhibitor. VS-7375 demonstrated potent inhibition of KRAS G12D-mutated-dependent signal transduction and cancer cell viability in vitro, as well as anticancer activity in human CRC and PDAC xenograft models alone and in combination with cetuximab. Collectively, the significant unmet medical need for treating tumors that harbor KRAS G12D mutations and the nonclinical results with VS-7375 strongly support a rationale for its development in patients with KRAS G12D-mutated cancers.VS-7375 is currently in clinical development in China under the name GFH375 by GenFleet Therapeutics Technology Co., Ltd (Shanghai, China). A first-in-human (FIH) clinical study of VS-7375 (Study GFH375X1101; NCT06500676) is ongoing as a multiphase study in China targeting patients with advanced KRAS G12D-mutated solid tumors, including NSCLC, PDAC, and CRC. The Phase 1 portion of that study involves dose escalation using a Bayesian optimal interval (BOIN) design to evaluate safety, tolerability, and pharmacokinetics (PK) across a range of doses, with initial endpoints focused on evaluating adverse events (AEs) and dose-limiting toxicities (DLTs). As of 17 January 2025, the 750 mg daily dose has been cleared for DLTs, and Study GFH375X1101 remains ongoing in the dose finding stage for patients with KRAS G12D-mutated cancers in China.This study is designed to evaluate the safety, tolerability, preliminary anticancer activity, and PK of VS-7375 in participants with advanced solid tumors harboring a KRAS G12D mutation outside China. The study will be conducted in 4 parts: Part A (single-agent dose escalation),Part B (single-agent dose expansion), Part C (VS-7375 combination dose escalation), and Part D (VS-7375 combination dose expansion).
A Phase 1a/1b First-in-human Multicenter Study to Assess the Efficacy and Safety of RGT-61159 for Treatment of Patients with Relapsed/Refractory Adenoid Cystic Carcinoma (ACC) or Colorectal Carcinoma (CRC)
This study will test the potential tumor-fighting effects of a daily medication called RGT-61159 for patients with advanced ACC or CRC, two types of cancer, when other treatments have stopped working or aren’t suitable. Patients will take RGT-61159 in 21-day cycles, starting at a dose of 6 mg. The study uses a dose-escalation plan, meaning patients will move to higher doses until the highest safe dose, or recommended Phase 2 dose (RP2D), is found. If certain side effects appear, more patients may be added at the current dose level to carefully check for safety and find the best dose for future studies.
A Phase 1a/1b Open-Label Study Evaluating the Safety Tolerability Pharmacokinetics and Efficacy of BBO-8520 in Subjects with Advanced KRASG12C Mutant Non-Small Cell Lung Cancer - the ONKORAS-101 Study
This is a Phase 1 study testing whether the new medicine BBO-8520 (a KRASG12C on/off inhibitor) is a safe and effective treatment option if given alone or together with another medicine called pembrolizumab (immunotherapy) for lung cancer patients whose tumors show changes in the KRAS gene. The study consist of two parts. In part 1, patients will be enrolled into one of five groups to receive the study medicine BBO-8520 alone. The study team will gradually increase the dose level of the study medicine for each group to find out the effective dose with fewer side effects. Some patients will be grouped to receive study medicine BBO-8520 together with pembrolizumab. In part 2, more patients will be included to receive the dose that was found to be effective while being safe. Patients who have previously received approved KRAS G12C inhibitors (ie, sotorasib and adagrasib) will be eligible. All patients will have blood samples taken to see how their bodies are handling the study medicines. The study team will have imaging scans taken for all patients to see how the study medicine is changing their tumor size. All patients will be closely monitored for side effects and safety concerns.
A Phase 1a/1b Trial of LY3962673 in Participants with KRAS G12D-Mutant Solid Tumors
This study is testing the tolerability, effectiveness, and potential for few side effects of the drug LY3962673 in patients with advanced solid tumors that have a KRAS G12D mutation, like pancreatic, colorectal, and lung cancer. In Phase 1a, the drug will be tested alone to see if it is well-tolerated and has few side effects. Some patients may receive different doses to check for side effects and how the drug works in the body. In Phase 1b, LY3962673 will be tested alone and with other standard treatments to find the best dose for these cancers. A committee will decide on dose increases based on the safety data.
A PHASE 1A/B OPEN-LABEL MASTER STUDY OF PF-07799544 AS A SINGLE-AGENT AND IN COMBINATION WITH OTHER TARGETED AGENTS IN PARTICIPANTS WITH BRAF-MUTANT MELANOMA AND OTHER SOLID TUMORS
This is a first-in-human, open-label, Phase 1a/b master protocol to evaluate safety,tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinicalactivity of PF-07799544 (also known as ARRY-134) as a single agent and in combinationwith other targeted agents in participants with advanced solid tumors.The mitogen activated protein kinase (MAPK) pathway plays a role in several key signalingand phosphorylation events that contribute to tumorigenesis. Inhibition of mitogen activatedextracellular kinase (MEK), along with rapidly accelerating fibrosarcoma (RAF) kinases, hasproven to be a successful transformative strategy for melanoma and other MAPKpathway-altered tumors. However, the duration of clinical benefit is limited by a narrowtherapeutic index, de novo and acquired resistance and poor brain penetration. PF-07799544is a next-generation, fully brain penetrant MEK inhibitor. Therefore, there is strong scientificrationale for PF-07799544 as a backbone for targeted therapy combination regimens.Phase 1a will be a monotherapy dose escalation of PF-07799544 to identify the maximumtolerated dose (MTDM) or recommended dose for expansion (RDEM) in participants withadvanced solid tumors whose disease has progressed on standard therapy.Phase 1b will be based on a master protocol design and will be comprised of multiplesubstudies, evaluating PF-07799544 with different combinatorial agents in participants withadvanced B-Raf protein kinase (BRAF) mutated melanoma or other solid tumors. Additional substudies may be added through amendment, and may include other study drugcombinations in other patient populations. Each substudy testing a new combination of drugswill be comprised of 2 parts: Part 1 to evaluate safety, tolerability, PK, and PD of thecombination of escalating doses of PF-07799544 with that of other targeted agents and Part 2to evaluate anti-tumor activity, safety, PK, and PD.
A Phase 1a/b Study Investigating the Safety Tolerability Pharmacokinetics Pharmacodynamics and Preliminary Antitumor Activity of BGB-58067 an MTA-Cooperative PRMT5 Inhibitor in Patients With Advanced Solid Tumors
This is an open-label, multicenter, first-in-human dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-58067 as monotherapy in patients with advanced solid tumors.
A Phase 1b Study of JNJ-78278343 a T-cell Redirecting Agent Targeting Human Kallikrein 2 (KLK2) in Combination with either JNJ-63723283 (cetrelimab) Taxane Chemotherapy or Androgen Receptor Pathway Inhibitors for Metastatic Castration- Resistant Prostate Cancer
This study will test the early effects of the immunotherapy drug JNJ-78278343, a bispecific antibody targeting KLK2 and CD3, combined with taxane chemotherapy or androgen receptor pathway inhibitor in adults with metastatic castration-resistant prostate cancer (mCRPC) who have already had at least one treatment. The study has two parts: Part 1, which will find the most effective dose by testing different amounts of the drugs in patients and Part 2 will include patients for each dose found to have few or no side effects and effective. A team of experts will watch for any safety issues and can stop the study if needed. The study has a Screening Period before treatment begins, a Treatment Period while the drugs are given, and an End of Treatment (EOT) visit when the treatment stops. Patients will be checked for side effects for up to 100 days after their last dose of cetrelimab or 30 days after their last dose of JNJ-78278343, depending on which comes later.
A Phase 1b Study of Nivolumab in Patients with Autoimmune Disorders and Advanced Malignancies (AIM-NIVO)
Nivolumab will be investigated at the Food and Drug Administration (FDA)-approved dose of480 mg intravenous (IV) every 4 weeks until unacceptable toxicity, disease progression, orcompletion of 2 years of therapy. If that dose and schedule have unacceptable toxicity, thenenrollment will cease for that particular disorder/severity group. Depending on accumulatedexperience from this study and other emerging literature, additional doses and schedules may beconsidered.This study is designed to enroll cohorts of up to 12 patients for each disease cohort who will betreated with nivolumab at the standard dose at each disease severity level. For each autoimmunedisorder, patients with different severity of the disease, as defined by disease-specific severityindices, will be assessed.Patients will initially be enrolled into the mild and moderate cohorts (exact designations in Table1). If nivolumab is well tolerated in this study population, then enrollment to more severecohorts will be opened following discussions with Cancer Therapy Evaluation Program(CTEP)/National Cancer Institute (NCI) and study teams at participating sites.
A Phase 1b Study to Evaluate the Safety Tolerability and Preliminary Efficacy of ATP150/ATP152 VSV-GP154 and Ezabenlimab (BI 754091) in Patients with KRAS G12D/G12V Mutated Pancreatic Ductal Adenocarcinoma
This is an open-label, phase 1b study comprising two parts (safety and immunogenicity part and randomized efficacy part) to evaluate the safety, tolerability, preliminary efficacy, and immunogenicity of a heterologous prime-boost vaccine (protein and viral vector) strategy, in which approximately 90 patients with resected KRAS G12D/G12V mutated pancreatic cancer and colorectal cancer after (neo-) adjuvant chemotherapy or chemoradiotherapy will be enrolled in the following treatment parts of the study:Part 1 (Safety and Immunogenicity Part) – PDAC and CRC patientsPart 2 (Efficacy Part) – PDAC patients only