Clinical Research Directory

Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants With Advanced Solid Tumors

The primary goal of this study is to assess the safety and tolerability of mRNA-4359 administered alone and in combination with pembrolizumab or ipilimumab and nivolumab.

Allogeneic WTX-212C in Advanced Solid Tumors

This is a multicenter, open-label, single-arm Phase I study to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of allogeneic WTX-212C, an investigational allogeneic engineered red blood cell (RBC)-based product, in patients with advanced solid tumors who have failed standard therapies or have no available standard treatment options. The study consists of a dose-escalation phase using a 3+3 design followed by a dose-expansion phase. Participants will receive allogeneic WTX-212C via intravenous infusion. Tumor assessments will be performed every 6 weeks according to RECIST 1.1.

A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors

Background: Small cell lung cancer and PARP inhibitor resistant tumors are aggressive cancers. Current treatments for people with these tumors yield little benefit. Researchers want to see if a combination of drugs can help. Objective: To find a safe combination of sacituzumab govitecan and berzosertib and to see if this will cause small cell lung cancer and PARP inhibitor resistant tumors to shrink. Eligibility: People ages 18 and older with a solid tumor, small cell lung cancer, or a homologous recombination-deficient cancer that is resistant to PARP inhibitors Design: Participants will be screened with: Standard clinical exams and tests EKG to test the heart Medical documentation to confirm cancer diagnosis Participants will get sacituzumab govitecan by vein on days 1 and 8 of each 21-day cycle. They will get berzosertib by vein on days 2 and 9. Treatment will continue as long as they can tolerate the drugs and their tumors are either stable or getting better. Before treatment and at least once per cycle, participants will have a physical exam and blood tests. Before treatment and every 2 or 3 cycles, they will have a CT scan. They will have a contrast agent injected into a vein for the scan. Participants will give blood and hair samples and tumor biopsies for research. Biopsies will be taken with a small needle under imaging guidance. After they stop treatment, participants will have a visit 1 month later. They will then be contacted by phone or email every 3 months for the rest of their lives....

HSK41959 With Standard Therapy in Solid Tumors With MTAP Deletion

This is a Phase Ib, open-label, multicenter study of HSK41959 tablets in combination with standard therapy in patients with MTAP-deficient advanced solid tumors. The study consists of dose-escalation and dose-expansion parts and is intended to evaluate the safety, tolerability, dose-limiting toxicity, maximum tolerated dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HSK41959 tablets when used together with standard therapy.

Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RMC-5127 as a monotherapy and in combination with either daraxonrasib or cetuximab in adults with KRAS G12V-mutant solid tumors.

An Open-label Study of SG1827 in Subjects With Advanced Solid Tumors

This is a Phase I, open-label, dose escalation and dose expansion study to Evaluate the Safety, Tolerability and Preliminary Efficacy of SG1827 in subjects with Advanced Solid Tumors, refractory or resistant to standard therapy, or without available standard or curative therapy.

A Phase I/II Study of CS2009 in Participants With Advanced Solid Tumors

This is a first-in-human (FIH), open-label, and multi-center Phase I/II study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of CS2009 as Monotherapy and Combination Therapy in Participants with Advanced Solid Tumors. The study is comprised of a Phase I dose escalation and Phase II dose expansion.

A Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Rilvegostomig in Adult Participants With Advanced Solid Tumors Previously Treated With Standard of Care Therapy

The purpose of this study is to determine the subcutaneous (SC) dose that gives rilvegostomig exposure comparable to the intravenous (IV) exposure, and to evaluate the pharmacokinetics (PK) and safety of SC rilvegostomig in adult participants with advanced solid tumors previously treated with standard of care therapy for whom immunooncology (IO) monotherapy would be deemed appropriate by the investigator.

Metarrestin (ML-246) in Subjects With Metastatic Solid Tumors

Background: Metastasis is the spread of cancer from one organ to a nonadjacent organ. It causes 90% of cancer deaths. No treatment specifically prevents or reduces metastasis. Researchers hope a new drug can help. It stops cancer cells from growing and spreading further and possibly shrink cancer lesions in distant organs. Objective: To find a safe dose of metarrestin and to see if this dose shrinks tumors. Eligibility: Adults age 18 and older with pancreatic cancer, breast cancer, or a solid tumor that has not been cured by standard therapies. Also, children age 12-17 with a solid tumor (other than a muscle tumor) with no standard therapy options. Design: Participants will be screened with: * blood tests * physical exam * documentation of disease confirmation or tumor biopsy * electrocardiogram to evaluate the heart * review of their medicines and their ability to do their normal activities Participants will take metarrestin by mouth until they cannot tolerate it or stop to benefit from it. They will keep a medicine diary. Participants will visit the Clinical Center. During the first month there are two brief hospital stays required with visits weekly or every other week thereafter. They will repeat some of the screening tests. They will fill out questionnaires. They will have tests of their cognitive function. They will have an electroencephalogram to record brain activity. They will have a computed tomography (CT) scan or magnetic resonance imaging (MRI). A CT is a series of X-rays of the body. An MRI uses magnets and radio waves to take pictures of the body. Adult participants may have tumor biopsies. Participants will have a follow-up visit 30 days after treatment ends. Then they will have follow-up phone calls or emails every 6 months for the rest of their life or until the study ends.

A Study of BG-C477 in Participants With Advanced Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BG-C477 alone and in combination with anticancer agents in participants with selected advanced solid tumors.

A First-in-human Study to Learn How Safe the Study Drug BAY3375968, an Anti-CCR8 Antibody, is, When Given Alone or in Combination With Pembrolizumab, How it Affects the Body, How it Moves Into, Through, and Out of the Body, and to Find the Best Dose in Participants With Advanced Solid Tumors

Researchers are looking for a better way to treat people who have advanced solid tumors. Advanced solid tumors are solid cancers that may have spread to nearby tissue, lymph nodes and/or to distant parts of the body and that are unlikely to be cured or controlled with currently available treatments. A new therapy available for advanced solid cancers is immunotherapy with PD-1/PD-L1 inhibitors. This drug class stimulates immune cells to kill cancer cells by blocking a protein called PD-1. Although PD-1/PD-L1 inhibitors have shown benefits in treatment of cancer, only a subset of patients benefit from the initial therapy, while in others the cancer comes back. One reason could be that the ability of the patients' immune systems to kill cancer cells is weakened by so-called regulatory T cells which have a suppressive effect on the immune system. The study treatment BAY3375968 is an antibody that binds to a protein called CCR8 which is located on the surface of regulatory T cells. This leads to a reduction in regulatory T cells and further inhibits their immune suppressive activity, so that the immune response against cancer can be strengthened as observed in animal models. Animal studies also showed that BAY3375968 may add more anti-cancer effect to immunotherapy with PD-1/PD-L1 inhibitors when used in combination. All of these previous observations need to be confirmed in humans. The main aims of this study are to find for BAY3375968 alone and in combination with pembrolizumab (a PD-1 inhibitor): * how safe it is * the degree to which overt medical problems caused by the treatment(s) can be tolerated * the highest amount of BAY3375968 that can be given alone or in combination with pembrolizumab. * how it moves into, through, and out of the body. To do this, researchers will collect and analyze data about: * the number and severity of participants' medical problems after taking their treatments * the best dose of BAY3375968 that can be given * the highest level in the blood (Cmax) and the total level (AUC) of BAY3375968. Doctors keep track of all medical problems (also called adverse events) that participants have during the study, even if they do not think that they might be related to the study treatment. The researchers will also study the activity of BAY3375968 alone and in combination with pembrolizumab against the cancer. The study will have 2 parts. Part 1 (dose escalation) focuses on tumor types that respond to immunotherapy. It will help to find the best dose for BAY3375968 alone and in combination with pembrolizumab that can be given in part 2. For this, the participants will receive one specific dose of several increasing BAY3375968 doses tested in part 1. Dose escalation of BAY3375968 alone will be done prior to the dose escalation of the combination with a fixed dose of pembrolizumab. The participants of part 2 (dose expansion), will receive the best dose of BAY3375968 alone or in combination with pembrolizumab found in part 1. This part of the study focuses on certain cancer types of the lung, breast, head and neck cancer, gastric cancer and melanoma. The total duration of the study will be approximately 4 years and 7 months. Each participant in the study will visit the study site twice before starting their treatment. Once the treatment starts, the frequency of visits is 5 times per week in the first treatment week and 1 to 3 times per month in later treatment periods. Another visit will be scheduled for the participants within 30 days after the last treatment in the study. During the study, the study team will: * take blood and urine samples * do physical and vital signs examinations * examine heart health using ECG and Echocardiogram * check the tumor status and if the participants' cancer has grown and/or spread using imaging techniques * take tumor samples * ask questions about the impact of the disease on the participants' general well-being and activities of daily life. About 90 days after the participants receive their last treatment and discontinued the study, the doctors will check the participants' health. In case a new anticancer therapy has been started, medical problems will be recorded via a phone call. The study team will continue to check the participants' cancer status about every 12 weeks until their cancer gets worse, the start of a new anti-cancer therapy, or withdrawal of consent. In addition, every 6 months for up to 24 months after the last participant left the study the study team will check the participants' survival and subsequent anticancer treatment by phone until the end of this study.

A First-in-human Study to Learn How Safe the Study Drug BAY2965501 is, Find the Best Dose (Single Drug & Combination), How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, How it Acts on Different Tumors in Participants With Advanced Solid Tumors

Researchers are looking for a better way to treat people who have advanced solid tumors. Advanced solid tumors are types of cancer that may have spread to nearby tissue, lymph nodes, and/or to distant parts of the body and that are unlikely to be cured or controlled with currently available treatments. This study focuses on certain types of skin cancer, kidney cancer, stomach cancer, and lung cancer. The study treatment BAY2965501 is currently under development as monotherapy or in combination for the treatment of people with advanced solid tumors. BAY2965501 blocks an enzyme in T-cells to activate them. T-cells are a type of immune cell that are known to have an anti-cancer effect and BAY2965501 is a potential new immunotherapy. The main purpose of this first-in-human study is to learn: • how safe different doses of BAY2965501 are when given as a single drug or in combination, • the degree to which medical problems caused by BAY2965501 when given as a single drug or in combination, can be tolerated (also called tolerability), • what maximum amount can be given as a single drug or in combination, and • how it moves into, through and out of the body as a single drug or in combination. To answer this, researchers will look at: • the number and severity of medical problems participants have after taking BAY2965501 as a single drug or in combination for each dose level. These medical problems are also referred to as adverse events. • the (average) total level of BAY2965501 in the blood (also called AUC) after intake of single and multiple doses • the (average) highest level of BAY2965501 in the blood (also called Cmax) after intake of single and multiple doses Doctors keep track of all medical problems that participants have during the study, even if they do not think the medical problem might be related to the study treatment. In addition, the researchers want to know if and how the participants' tumors change after taking BAY2965501. The study will have two parts. The first part, called dose escalation, is done to find the most appropriate dose that can be given in the second part. For this, participants will be assigned to receive one of the planned doses and schedules of BAY2965501 as single drug or participants will be assigned to one of the increasing doses of BAY2965501 in combination with 200mg pembrolizumab. Additionally, platinum based chemotherapy as decided by the treating investigator will be given within the first months (at minimum 2 cycles and up to 6 cycles maximum). Here participants will receive BAY 2965501 in combination with pembrolizumab and platinum based chemotherapy. All participants will take BAY2965501 by mouth. Additionally, in combination group 1, pembrozilumab will be given as infusion using a small tube that goes into your vein. In combination group 2, pembrolizumab and platinum based chemotherapy will be given as infusion using a small tube that goes into your vein. In the second part, called dose expansion, all participants in the single drug group will receive up to 2 of the most appropriate doses of BAY2965501 from the 1st part as tablet by mouth. The participants in the combination groups (group 1: + pembrozilumab; group 2: + pembrolizumab and platinum based chemotherapy) will receive the most appropriate dose of BAY2965501 from the first part. Participants in both parts of the study, will take the study treatment until the tumor gets worse (also known as 'disease progression'), or until the participants have medical problems. In general, the study treatment is planned for a maximum of 35 cycles. Each participant will be in the study for several months, including a screening phase of up to 28 days, few months of treatment depending on the participant's benefit, and a follow up phase after the end of treatment. Participants in part two will be assigned to one of 3 groups depending on cancer characteristics.During the study, the study team will: • take blood and urine samples • do physical examinations • check vital signs such as blood pressure, heart rate, body temperature • examine heart health using ECG (electrocardiogram) • check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and, if needed, bone scan • take tumor samples (if required) The treatment period ends with a visit no later than 7 days after the last BAY2965501 dose in the single drug and combination group. About 30 and 90 days after the last dose and every 12 weeks thereafter, the study team will check the participants' health and any changes in cancer. This follow-up period ends with worsening of the cancer, start of new anti-cancer therapy, or until the participant leaves the study.

A Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)

Researchers are looking for a better way to treat people who have solid tumors with HER2-activating mutations. Before a treatment can be approved for people to take, researchers do clinical trials to better understand its safety and how it works. In this trial, the researchers want to learn how well BAY2927088 (sevabertinib) works in people with different types of solid tumors with HER2 mutations. These include tumors in the colon or rectum, the uterus and the cervix (lower part of the uterus), the breast, the bladder, and the biliary tract (includes gall bladder and bile ducts) as well as other types of solid tumors with the exception of people with advanced non-small cell lung cancer (NSCLC). Solid tumors may have specific changes or mutations to a gene called human epidermal growth receptor-2 (HER2). This leads to the formation of an abnormal form of HER2 protein in the cancer cells, resulting in increased cell growth. The study treatment, BAY2927088, is expected to block the abnormal HER2 protein which may stop the spread of cancer. The trial will include about 111 participants who are at least 18 years old. All the participants will take 20 mg of BAY2927088 as tablets by mouth. The participants will take treatments in 3-week periods called cycles. These 3-week cycles will be repeated throughout the trial. The participants can take BAY2927088 until their cancer gets worse, until they have medical problems, or until they leave the trial. During the trial, the doctors will take imaging scans of different parts of the body to study the spread of cancer and will check heart health using echocardiogram or cardiac magnetic resonance imaging (MRI) and electrocardiogram (ECG). The doctors will also take blood and urine samples and do physical examinations to check the participants' health. They will ask questions about how the participants are feeling and if they have any medical problems.

Trial to Evaluate the Safety and Preliminary Efficacy of GEN1079 in Participants With Advanced Solid Tumors

The purpose of this trial is to learn about the safety and effectiveness of the antibody GEN1079 in participants with certain types of cancer. The trial has multiple parts. The first part of the trial tests different doses of GEN1079 to find out if it is safe and determine what are the best doses to use. The second and third parts continue to test the safety of and whether GEN1079 works in additional participants with specific cancer types and at doses chosen based on results from the previous parts of the trial. For each participant, the trial will last approximately 33 to 67 weeks but this may vary for each person. This includes up to 21 days for screening prior to receiving trial treatment, approximately 6 to 12 weeks of treatment (the duration of treatment may vary for each participant), and approximately 24 to 52 weeks of follow up after trial treatment ends (the duration of follow up may vary for each participant). During the screening, tumor tissue either collected prior to this trial or freshly collected during screening will be provided by all participants. Participation in the trial will require visits to the site, with more frequent visits at the start of treatment and then less frequent visits afterwards. At site visits, there will be various tests (such as blood draws) and procedures (such as recording of heart activity, computed tomography \[CT\] scans) to monitor whether the treatment is safe and effective. All participants will receive active drug; no one will be given placebo.

First-in-Human Study of ATX-295, an Oral Inhibitor of KIF18A, in Patients With Advanced or Metastatic Solid Tumors, Including Ovarian Cancer

The goal of this study is to identify a safe and tolerated dose of the orally administered KIF18A inhibitor ATX-295. In addition, this study will evaluate the pharmacokinetics, pharmacodynamics and preliminary antitumor activity of ATX-295 in patients with advanced solid tumors and ovarian cancer.

A Study to Evaluate the Safety and Efficacy of MK-3120 in Participants With Advanced Solid Tumors (MK-3120-002)

Researchers are looking for new ways to treat people with certain advanced solid tumors. Advanced means the cancer has spread to other parts of the body and cannot be removed with surgery. Solid tumors are cancers mostly in body organs and tissues, not in the blood or other body liquids. The main goal of this study is to learn about the safety of MK-3120 and if people tolerate it.

First-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer

OKI-219-101 is a Phase 1a/1b, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and efficacy of OKI-219 as monotherapy and in combination with other anti-cancer drugs. Phase 1a (Part A) will investigate escalating doses of OKI-219 monotherapy, and Phase 1b will investigate OKI-219 (at a tolerated dose determined in Part A) in combination with fulvestrant (Part B), trastuzumab and tucatinib (Part C), atirmociclib (Part D), and ribociclib and fulvestrant (Part E). Participants will continue to receive study treatment until disease progression, intolerable toxicity, or other study treatment withdrawal criteria are met.

A Study of JNJ-87890387 for Advanced Solid Tumors

The purpose of this study is to determine safety and recommended phase 2 dose(s) (RP2Ds) of JNJ-87890387 and to determine the safety of JNJ-87890387 at the RP2D(s).

Bicycle Continued Access Protocol (BiCAP) for Participants Receiving a Bicycle Investigational Product

BiCAP-201 trial offers continued access to Bicycle investigational product treatments zelenectide pevedotin, nuzefatide pevedotin, and BT7480 for participants currently receiving and deriving clinical benefit from one of these treatments in a Bicycle Therapeutics-sponsored clinical trial. Bicycle Therapeutics will continue to monitor longer term safety of these treatments.

A Trial to Find Out How Safe REGN7075 is and How Well it Works in Combination With Cemiplimab for Adult Participants With Advanced Cancers

This study is researching an investigational drug called marlotamig (REGN7075) by itself and in combination with cemiplimab with or without chemotherapy. The study is focused on patients with certain solid tumors that are in an advanced stage. The aim of the study is to see how safe and tolerable marlotamig is by itself and in combination with cemiplimab (with or without chemotherapy), and to find out what is the best dose of marlotamig to be given to patients with advanced solid tumors when combined with cemiplimab (with or without chemotherapy). Another aim of the study is to see how effective marlotamig by itself, or in combination with cemiplimab (with or without chemotherapy), is at treating cancer patients. The study is also looking at: * Side effects that may be experienced by people taking marlotamig by itself and in combination with cemiplimab with or without chemotherapy * How marlotamig works in the body by itself and in combination with cemiplimab with or without chemotherapy * How much marlotamig is present in the blood when given by itself and in combination with cemiplimab with or without chemotherapy * To see if marlotamig by itself and in combination with cemiplimab with or without chemotherapy works to treat cancer by controlling the proliferation of tumor cells to shrink the tumor * Whether the body makes antibodies against the study drugs (marlotamig and cemiplimab) (which could make the drug less effective or could lead to side effects)

A Study of BMS-986490 With or Without Bevacizumab in Advanced Solid Tumors

This is a study of BMS-986490 as a monotherapy and in combination with bevacizumab in participants with select advanced solid tumors known to express CEACAM5.

A Trial to Investigate the Safety of E303 in Participants With Advanced Refractory Solid Tumors

This is a Phase I trial to evaluate the safety, tolerability and efficacy of nectin-4 targeting antibody-drug conjugate (SBE303) in participants with advanced solid tumors

Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RAS(ON) inhibitors in combination with ivonescimab in adults with advanced or metastatic solid tumors with a RAS mutation.

Safety,Tolerability, Pharmacokinetics, and Efficacy of YL211 in Patients With Advanced Solid Tumors

This is a multicenter, open-label, Phase 1 study. The study will enroll subjects with advanced solid tumors. It consists of six parts. Objectives for Dose-Escalation Parts (Part 1 and Part 4) To evaluate the safety and tolerability of YL211 as monotherapy in patients with selected advanced solid tumors (Part 1) and in combination with pembrolizumab in patients with second or third line locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) (Part 4) To determine the maximum tolerated dose (MTD) and select the recommended expansion dose(s) (RED(s)) of YL211 as monotherapy in patients with advanced solid tumors (Part 1) and in combination with pembrolizumab in patients with second line locally advanced unresectable or metastatic non-squamous NSCLC (Part 4) Objectives for Backfill Enrollment Parts (Part 2 and Part 5) To better estimate and characterize the safety and efficacy of YL211 as monotherapy in patients with metastatic colorectal cancer (mCRC) or locally advanced unresectable or metastatic NSCLC (Part 2) and in combination with pembrolizumab in patients with previously untreated locally advanced unresectable or metastatic non-squamous NSCLC (Part 5) To select the RED(s) of YL211 as monotherapy in patients with metastatic colorectal cancer (mCRC) or locally advanced unresectable or metastatic NSCLC (Part 2) and in combination with pembrolizumab in patients with previously untreated locally advanced unresectable or metastatic non-squamous NSCLC (Part 5) Objectives for the Dose-Expansion Parts (Part 3 and Part 6) To further characterize the safety and efficacy of YL211 as monotherapy (Part 3) in patients with locally advanced unresectable or metastatic non-squamous or squamous NSCLC and in combination with pembrolizumab in patients with previously untreated locally advanced unresectable or metastatic non- squamous NSCLC (Part 6) To compare the clinical activity of YL211 in combination with pembrolizumab against pembrolizumab, pemetrexed, and platinum-based chemotherapy (cisplatin or carboplatin) in participants with previously untreated advanced unresectable or metastatic non-squamous NSCLC (Part 6)