A Phase 1/2 Open-Label Study to Evaluate the Safety Tolerability Pharmacokinetics and Efficacy of TNG260 as Single Agent and in Combination with an anti-PD-1 Antibody in Patients with STK11-Mutated Advanced Solid Tumors
This is a first-in-human Phase 1/2, open-label, multicenter, dose-escalation and -expansionstudy designed to determine the MTD of TNG260 as single agent and in combination withpembrolizumab, to determine the RP2D(s) of the combination, and to evaluate the safety andtolerability, PK, and antineoplastic activity of escalating oral doses of TNG260 whenadministered alone and with a standard dose of pembrolizumab in participants with locallyadvanced or metastatic STK11-mutated solid tumors who have progressed on at least 1 lineof standard therapy or are ineligible for standard therapies.In Phase 1 (dose escalation), at least 3 DLT-evaluable participants will be enrolled insequentially escalating dose cohorts to determine the MTD of single agent TNG260, theMTD of the combination of TNG260 and pembrolizumab, and the RP2D(s) of TNG260 incombination with a standard dose of pembrolizumab. The dose escalation of TNG260 will beguided by two BLRMs based on any DLTs observed in the first cycle (ie, the first 21 days) ofthe single agent therapy and the second cycle for the combination therapy.Participants in Phase 2 (dose expansion) will be dosed at the RP2D(s) determined fromPhase 1 based on demonstrated tolerability, together with available PK data and results oftarget engagement studied during Phase 1 (or other measures including PD and efficacy), asapplicable. Three Phase 2 combination expansion arms (TNG260 in combination withpembrolizumab) will enroll up to approximately 30 participants each.
A Phase 1/2 Study of LY3537982 in Patients with KRAS G12C-Mutant Advanced Solid Tumors
Study LOXO-RAS-20001 is a first-in-human, multicenter, open-label Phase 1/2 study to evaluate the safety, tolerability, and preliminary efficacy of oral LY3537982 as monotherapy and as part of combination therapy in patients with KRAS G12C-mutant advanced solid tumor types, including but not limited to NSCLC and CRC.This study includes 2 parts, Phase 1a dose escalation (Part A) followed by a Phase 1b dose expansion (Part B-E). The Phase 1a dose escalation LY3537982 monotherapy cohort will enroll any eligible patient with KRAS G12C-mutant advanced solid tumor. Once the LY3537982 monotherapy RP2D (RP2DM) is established, Phase 1b dose expansion will begin and include 10 cohorts (NSCLC, Cohorts B1–B6; CRC, Cohorts C1–C2; other solid tumors [except NSCLC and CRC], Cohort D1; KRAS G12C-mutant advanced NSCLC who have previously been treated with a KRAS G12C inhibitor, Cohort E1) to further evaluate safety and clinical activity.KRAS G12C mutations will be identified through standard of care testing as routinely performed at each participating site utilizing material collected prior to patient consent to this protocol. Molecular assays utilized for enrollment are required to be performed in Clinical Laboratory Improvement Amendments (CLIA), International Organization for Standardization/International Electrotechnical Commission (ISO/IEC), College of American Pathologists (CAP), or other in a similarly certified laboratory.
A PHASE 1/2 STUDY OF REGN5678 (ANTI-PSMAXCD28) WITH OR WITHOUT CEMIPLIMAB (ANTI-PD-1) IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER AND OTHER TUMORS ASSOCIATED WITH PSMA EXPRESSION
This is an open-label, phase 1/2, first-in-human (FIH) study evaluating safety, tolerability, PK, and anti-tumor activity of REGN5678 (anti- PSMAxCD28) alone and in combination with cemiplimab (anti-PD-1) in treatment-experienced metastatic castration-resistant prostate cancer (mCRPC).There are two parts of the study:? Dose escalation: During dose escalation, patients will receive a 3- week monotherapy lead-in of REGN5678 at the assigned dose level (DL) administered intravenously (IV) weekly (QW) followed by combination therapy of REGN5678 at the assigned DL IV QW and cemiplimab 350 mg IV every 3 weeks (Q3W).? Dose Expansion: During dose expansion, patients will receive combination therapy of REGN5678 at the assigned DL (eg, maximum tolerated dose [MTD]/recommended phase 2 dose [RP2D]) IV QW and cemiplimab 350 mg IV Q3W without a 3- week monotherapy lead-in of REGN5678.Dose expansion cohort(s) will be enrolled after identification of the REGN5678 MTD in combination with cemiplimab and/or RP2D. Prior to enrollment of an expansion cohort, 3 to 6 additional patients will be enrolled at that DL without a 3-week monotherapy lead-in of REGN5678 to further evaluate safety and biologic activity (dose escalation cohorts designated with an asterisk [*cohorts]).Safety evaluations will be conducted at each study drug dosing visit. Radiographic response assessment will be performed every 6 weeks from cycle 1 (C1D42/C2D1) up to cycle 4 (including patients who receive the initial 3-week monotherapy lead-in of REGN5678) and every 12 weeks thereafter.Investigators should continue treating patients with study drug until confirmed disease progression, elective discontinuation for response, per modified PCWG3, intolerable adverse events (AEs), withdrawal of consent, or other study withdrawal criterion is met. Patients who do not withdraw consent will then be expected to continue off-treatment follow-up procedures.
A Phase 1/2 Study of the Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor NVL-655 in Patients with Advanced NSCLC and Other Solid Tumors (ALKOVE-1)
A Phase 1/2 Study of the Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor NVL-655 in Patients with Advanced NSCLC and Other Solid Tumors (ALKOVE-1)
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 Multicenter Open-Label First in Human Study to Assess the Safety Tolerability Pharmacokinetics and Preliminary Antitumor Activity of DB-1305 in Subjects with Advanced/Metastatic Solid Tumors
This is a multicenter, non-randomized, open-label, multiple-dose, first in human (FIH) study. The study consists of two parts: Part 1 adopts an accelerated titration at first dose level followed with classic "3+3" design to identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D); Part 2 is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors at the MTD/the RP2D. This study will enroll subjects with advanced/unresectable, recurrent, or metastatic malignant solid tumors.
A Phase 1b Multicenter Study to Determine the Dose Safety Efficacy and Pharmacokinetics of TRK-950 when Used in Combinations with Selected Anti-Cancer Treatment Regimens in Patients with Selected Advanced Solid Tumors
This study is an open-label, Phase 1b study evaluating TRK-950 in combination with 1) FOLFIRI or 2) Gemcitabine / Cisplatin or 3) Gemcitabine / Carboplatin or 4) Ramucirumab/Paclitaxel or 5) PD1 inhibitors (Nivolumab or Pembrolizumab) or 6) Imiquimod Cream for subcutaneous lesions 7) Bevacizumab or 8) Nivolumab / Ipilimumab in Patients with Selected Advanced Solid Tumors. The objectives of this study are to determine the safety, tolerability, MTD, recommended Phase 2 dose (RP2D), PK, and preliminary anti-tumor activity of TRK-950 when used in combination with other treatment regimens.
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
A Phase 1b/2 Open-label Umbrella Study to Evaluate Safety and Efficacy of Elacestrant in Various Combinations in Patients with Metastatic Breast Cancer (ELEVATE)
This is a multicenter, Phase 1b/2 trial. The Phase 1b part of the trial aims to determine the RP2D of elacestrant when administered in combination with alpelisib, everolimus, palbociclib, and ribociclib. The Phase 2 part of the trial will evaluate the efficacy and safety of the various combinations in patients with ER+/HER2- advanced/metastatic breast cancer.
A Phase 1b/2 Randomized Open-Label Study Investigating the Efficacy and Safety of LBL-007 Plus Tislelizumab in Combination With Bevacizumab Plus Fluoropyrimidine Versus Bevacizumab Plus Fluoropyrimidine as Maintenance Therapy in Patients With Unresectable or Metastatic Microsatellite Stable/Mismatch Repair Proficient Colorectal Cancer
This is a Phase 1b/2 study to investigate the efficacy and safety of LBL-007 plus Tislelizumab when administered in combination with bevacizumab plus fluoropyrimidine to participants with colorectal cancer.