Clinical Research Directory

A Study to Evaluate the Safety, Pharmacokinetics, and Activity of Enzelkitug as a Single Agent and in Combination With Checkpoint Inhibitor in Participants With Locally Advanced or Metastatic Solid Tumors

This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of enzelkitug when administered as a single agent and in combination with atezolizumab or pembrolizumab in adult participants with locally advanced or metastatic solid tumors, including non small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, triple-negative breast cancer (TNBC), esophageal cancer, gastric cancer, cervical cancer, colorectal cancer (CRC), urothelial carcinoma (UC), clear cell renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Participants will be enrolled in 2 stages: dose escalation and dose expansion.

Moderated Hypofractionated Online Adaptive Radiotherapy in Cervical Cancer

The most common external beam radiotherapy fractionation scheme for cervical cancer is 45-50.4 Gy delivered in 25-28 fractions. However, prolonged treatment duration can lead to insufficient availability of medical resources. We hope to assess the safety and efficacy of moderated hypofractionated online adaptive radiotherapy in combination with brachytherapy in patients with cervical cancer in a multicenter study.

Engineered Immune Effectors Against Cervical Cancer

The primary objective of this study is to evaluate the safety of cervical cancer specific engineered immune effectors (CC-EIEs). The secondary objectives are to evaluate the rate of successful CC-EIE generation in vitro and determine the anti-CC efficacy.

Intervention of CAR-T Against Cervical Cancer

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of CAR T cells immunotherapy in patients who have GD2, PSMA, Muc1, Mesothelin or other markers positive cervical cancer. Another goal of the study is to learn more about the persistence and function of CAR T cells in the body.

Triage of Advanced Cervical Cancer Through Immunotherapy Induction (TRACTION)

To learn if MGD019 can help to control cervical cancer in patients who have yet to receive treatment.

Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers

The primary purpose of this study is to assess the safety and tolerability of AB598 in participants with advanced malignancies.

Study of RGT-490 in Patients With PIK3CA-Mutated Advanced Solid Tumors

This is a phase 1/1b, open-label, multicenter study consisting of sequential parts designed to evaluate the safety, tolerability, and effects pharmacokinetic (PK) profile, and antitumor activity of RGT-490, an investigational oral therapy, in adults with locally advanced or metastatic solid tumors including breast cancer. Participants enrolled in the study have advanced disease that is not amendable to curative treatment and whose tumors harbor alterations in the PI3KCA gene.

A Beta-only IL-2 ImmunoTherapY Study

This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors.

Development of Systems and Education for Cervical Cancer Prevention (DOSE-CC)

Cervical cancer disproportionately impacts those who have not accessed screening or follow-up. Universal screening has the potential to decrease the overall burden of cervical cancer. However, more than half of the individuals who develop cervical cancer have not been screened in more than 5 years, and 20% did not follow-up after an abnormal result. To address this problem, the investigators will adapt and test an intervention to improve cervical screening and follow-up in three different settings: Northeastern US urban inner city (Boston), Southeastern US suburban (Florida), and remote west, rural (Hawaii). Our research group previously developed a successful intervention to improve primary cervical cancer prevention, which will be adapted for cervical cancer screening. The intervention combines education and quality improvement methods using a mechanism called Performance Improvement Continuing Medical Education. This type of intervention is attractive to clinicians because they are able to improve their cancer prevention practices while fulfilling requirements for maintaining board certification. When applied to primary prevention, the intervention improved rates by over 10 percentage points, and gains continued for over 4 years after the intervention concluded. The goal of the proposed research is to adapt the intervention to cervical cancer screening, and to evaluate its effectiveness in improving cervical cancer screening and follow-up after abnormal results. The proposed intervention represents an innovative and scalable model for promoting cancer prevention and screening activities by clinicians. Unlike programs that increase administrative burdens on busy clinicians, the proposed intervention allows clinicians to improve cancer prevention practices while simultaneously fulfilling requirements to maintain their board certification and improving the quality of cancer prevention care. It therefore has great potential for widespread dissemination.

Hydrogel Spacer During Definitive Radiotherapy for Cervical Cancer

This prospective, single-center study will evaluate the feasibility, spatial stability, and dosimetric effects of an absorbable hydrogel spacer placed between the cervix/vagina and rectum before definitive radiotherapy for cervical cancer. Approximately 30 participants will receive hydrogel spacer implantation before the first fraction of external beam radiotherapy (EBRT), followed by standard definitive radiotherapy including EBRT and image-guided brachytherapy (IGBT). Serial magnetic resonance imaging (MRI) and computed tomography (CT) will be used to assess spacer position, thickness, and stability throughout treatment. Radiation doses to the rectum and other organs at risk will be evaluated across the full course of radiotherapy. The primary objective is to assess the effect of the hydrogel spacer on cumulative rectal dose while maintaining adequate target coverage. Procedure-related safety and feasibility will also be evaluated.

A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Cancer (MK-2870-036/TroFuse-036/GOG-3123/ENGOT-cx22)

Researchers are looking for new ways to treat metastatic cervical cancer. Cervical cancer is cancer in the cervix, the lower part of the uterus (womb). Metastatic means the cancer has spread to other parts of the body. Researchers want to learn about giving the study medicine sacituzumab tirumotecan (also called sac-TMT or MK-2870) along with pembrolizumab and bevacizumab treatments. Sac-TMT is an antibody drug conjugate, which is a type of medicine that attaches to specific targets on cancer cells and delivers treatment to destroy those cells. The goals of this study are to learn: * About the safety of sac-TMT with pembrolizumab and bevacizumab, and if people tolerate them when given together, and * If people who receive sac-TMT and pembrolizumab, with or without bevacizumab, live longer overall or without their cancer getting worse as compared to those who receive standard treatment

Adaptive Radiotherapy for Safe Hypofractionation

This phase II, registry-based cohort-multiple randomized controlled trial (cmRCT) evaluates whether daily online adaptive radiotherapy (ART) enables the safe delivery of hypofractionated, iso-biologically equivalent (EQD2) external beam radiotherapy compared with standard-of-care (SOC) fractionation. Conventional radiotherapy requires generous planning target volume (PTV) margins to account for inter-fraction anatomical variation, which increases radiation exposure to surrounding organs at risk (OARs) and may contribute to toxicity. Modern ART platforms using daily on-table imaging (kV-CBCT or MRI guidance) allow real-time contour adaptation and online plan re-optimization based on same-day anatomy. This approach enables margin reduction while maintaining target coverage and may permit safe hypofractionation. Eligible patients enrolled in an institutional prospective registry will be randomized (1:1) to receive either SOC radiotherapy or hypofractionated ART across multiple pelvic disease strata (post-prostatectomy prostate cancer, intact prostate cancer, endometrial cancer, cervical cancer, and rectal cancer). The primary objective is to demonstrate non-inferiority of hypofractionated ART compared with SOC in terms of cumulative incidence of Grade ≥2 toxicity (CTCAE v5). Secondary outcomes include acute and late toxicity, oncologic outcomes (progression-free survival, locoregional failure, distant metastases, overall survival), patient-reported outcomes, treatment efficiency, and dosimetric parameters. A Bayesian monitoring framework with pre-specified safety and futility stopping rules will be used to ensure patient safety and clinical equipoise throughout the trial.

C2001P-CS3: Testing the Feasibility of Different HPV Screening and Care Strategies for Women Living With HIV

The overall goal of this study is to inform the design and establish feasibility for a future clinical trial to determine the optimal management of women living with HIV (WLWH) with high-risk human papillomavirus (hrHPV) detected on HPV-based cervical cancer screening. WLWH have a higher diversity of anogenital HPV types causing cervical high-grade squamous intraepithelial lesions (hHSIL) and invasive cancer compared to women without HIV. While there is consensus that women testing positive for HPV 16 and/or 18 should be immediately managed and treated, optimal management strategies for women with other hrHPV types (non-16/18) are not well defined. This prospective cohort study will enroll WLWH undergoing cervical cancer screening using primary HPV testing. Women will self-collect vaginal specimens for hrHPV testing using the Abbott Alinity m HPV assay, which provides extended HPV genotyping and a proxy for HPV viral load based on cycle threshold (CT) values. Women with hrHPV detected will return for further evaluation and treatment as indicated. A subset of women will return at Month 6 for repeat evaluation. The study will evaluate feasibility for a future trial by examining recruitment, retention, return for evaluation, and completion of treatment. It will also explore management strategies for women with non-16/18 hrHPV based on extended genotyping and HPV viral load compared to standard of care approaches using visual inspection with acetic acid (VIA).

Inactivated KAWAI Bacteria for Diarrhea Prevention During Pelvic Radiotherapy in Postoperative Cervical Cancer

This is a multicenter, randomized, double-blind, placebo-controlled study. The purpose of this study is to evaluate whether an oral probiotic supplement (KAWAI inactivated bacteria) can reduce the side effects (especially diarrhea) caused by pelvic external beam radiation therapy in patients who have undergone surgery for cervical cancer. Women aged 18 to 70 who have been diagnosed with cervical cancer, have recently undergone surgery, and are scheduled to receive only pelvic external radiation therapy may be eligible to participate. Participants will be randomly assigned (like flipping a coin) in a 1:1 ratio to receive either the KAWAI supplement or a placebo. They will take the study product starting 7 days before radiation therapy and continue until 6 weeks after the radiation therapy ends. Researchers will closely monitor and compare the occurrence of diarrhea and other side effects between the two groups to see if the KAWAI supplement is safe and effective in improving patients' quality of life during radiotherapy. A total of 100 participants are expected to be enrolled.

E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers

This is a phase II clinical trial to assess the clinical activity of immunotherapy with E7 TCR-T cells for metastatic HPV-associated cancers. HPV-associated cancers in include cervical, throat, penile, vulvar, vaginal, anal, and other cancers. Participants will receive a conditioning regimen, E7 TCR-T cells, and aldesleukin. Clinical response to treatment will be determined.

A Phase 1/2 Trial of TER-2013 in Patients With Solid Tumors Harboring AKT/PI3K/PTEN Pathway Alterations

This is a Phase 1/2, open-label, multicenter study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of TER-2013 in patients with advanced solid tumors harboring AKT/PI3K/PTEN pathway alterations.

E7 T-cell Receptor (TCR) -T Cell Induction Therapy for Locoregionally Advanced HPV-associated Cancers

The goal of this study is to determine the feasibility of administration of a single dose of E7 TCR-T cells as induction therapy prior to definitive treatment (chemoradiation or surgery) of locoregionally advanced HPV-associated cancers. The intent of E7 TCR-T cell treatment is to shrink or eliminate tumors and thereby facilitate definitive therapy and increase overall survival. This study seeks to determine 1) if E7 TCR-T cells can be administered without undue delay in definitive treatment, 2) the tumor response rate to E7 TCR-T cell treatment, and 3) the disease-free survival rate at 2 and 5 years. Participants will undergo an apheresis procedure to obtain T cells that will be genetically engineered to generate E7 TCR-T cells. They will receive a conditioning regimen, a single infusion of their own E7 TCR-T cells, and adjuvant aldesleukin. Participants will follow up to assess safety and determine tumor response and will return to their primary oncology team for definitive therapy.

KK-LC-1 TCR-T Cell Therapy for Gastric, Breast, Cervical, and Lung Cancer

This is a phase I clinical trial to determine the maximum tolerated dose (MTD) of KK-LC-1 TCR-T cells for the treatment of metastatic cancers that express KK-LC-1. Participants will receive a conditioning regimen, KK-LC-1 TCR-T cells, and aldesleukin. The safety profile and clinical response to treatment will be determined.

A Study of MGC026 in Participants With Advanced Solid Tumors

The study is designed to understand the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of vobramitamab tavatecan (MGC026) in participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors The study has a dose escalation portion and a cohort expansion portion in Module A of the study. Combination therapy with pembrolizumab will occur in Module B of the study Participants will receive vobramitamab tavatecan by intravenous (IV) infusion. The dose of vobramitamab tavatecan will be assigned at the time of enrollment. Pembrolizumab will be administered at 200 mg every 3 weeks. Participants may receive up to 35 treatments if there are no severe side effects and as long as the cancer does not get worse. Participants will be monitored for side effects, and progression of cancer, have blood samples collected for routing laboratory work, and blood and tumor samples collected for research purposes.

Benefits of cinEmA Sessions During Radio-chemoTherapy on Outcomes of Patients With ceRvIcal canCEr

The BEATRICE (Benefits of cinEmA Sessions During Radio-chemoTherapy on Outcomes of Patients With ceRvIcal canCEr) study protocol aims to explore the psychological and medical benefits of cinema therapy during chemotherapy sessions for cervical cancer patients undergoing radiochemotherapy (RTCT). The study builds on prior research indicating the efficacy of art-based and immersive interventions, such as virtual reality, in reducing anxiety, distress and body symptoms in oncology patients. With a focus on personalizing cancer care, this study utilizes an immersive multimedia room where patients weekly can watch curated films during chemotherapy sessions. Endpoints include psychological outcomes, such as state anxiety, quality of life, and affective states, body perceptions, as well as medical outcomes, such as perceived treatment duration, salivary alpha-amylase levels (a stress biomarker), and clinical responses over time. This randomized controlled trial spans 24 months, including recruitment, data collection, and analysis. Patients are assessed at three timepoints: before, immediately after, and seven days post-chemotherapy infusion, using validated psychological and quality-of-life measures. Salivary samples will also be analyzed to evaluate stress levels before and immediately after chemotherapy. The BEATRICE study integrates technological and artistic innovation into patient care, aligning with a broader movement towards empathetic and uplifting oncology practices.

Identifying and Addressing Barriers to Retention in the Cervical Cancer Treatment Cascade Among Women With HIV in South Africa: Part 2

The investigators will conduct the formative work that is necessary to develop a novel, multi-level intervention (inclusive of patient- and provider-level components), which will increase awareness of and modify the complex, intersecting factors that contribute to cervical cancer development among cisgender women with HIV (WWH). In Aim 1a, the investigators will explore the multi-level barriers and facilitators to follow-up appointment attendance among WWH who have had a recent high-risk abnormal Pap smear in the past six months, via qualitative interviews with WWH who have either attended at least one follow-up visit (n\<10) or have not yet attended a follow-up visit (n\<10). In Aim 1b, the investigators will explore provider awareness of the HIV-cervical cancer relationship and perspectives on barriers to retention in care via qualitative interviews (n\<8). For Aim 2, The study team will leverage the Aim 1 data, develop a patient-level intervention (2 sessions) and a provider toolkit, with the goal of increasing retention in care among WWH who are at heightened risk for cervical cancer. In Aim 3a, the investigators will test the feasibility and acceptability of the intervention in a pilot randomized control trial (RCT) (n\<60). The study team will also assess (1) changes in self-efficacy to attend cervical cancer-related healthcare appointments at baseline, end of intervention, and three-months post-baseline, (2) the proportion of women who attend a follow-up appointment, and, of those participants, (3) the proportion of women who complete the next phase of treatment. In Aim 3b, the investigators will explore the feasibility of intervention implementation in the clinic and acceptability of the provider-level intervention components in qualitative interviews with providers and clinic staff (n\<10).

A Study of HER3-DXd in Subjects With Locally Advanced or Metastatic Solid Tumors

This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced unresectable or metastatic solid tumors. The study is enrolling cohorts of participants with melanoma \[cutaneous/acral\], squamous cell carcinomas of the head and neck (SCCHN), HER2-negative gastric cancer ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, prostate cancer, second-line gastric cancer, lung cancer, and breast cancer.

Feasibility of the "One-Finger Technique" for Identifying the Upper Left Ureter During Para-Aortic Lymphadenectomy

Para-aortic lymphadenectomy plays an important role in the surgical treatment of major gynecological malignancies (ovarian, endometrial, and cervical cancer). Identifying bilateral ureters is a crucial step, and dissecting the upper left ureter is particularly challenging with no standardized method. This study introduces an anatomical technique called the "One-Finger Technique" for this purpose. This prospective, single-arm exploratory study aims to evaluate the feasibility and safety of the "One-Finger Technique" during open para-aortic lymphadenectomy.

Radiotherapy for Gynecologic Cancer With Up to 10 Active Metastatic Lesions

OLIGYNE-10 RT is an international registry of adults with gynecologic cancer and a limited number of active sites of cancer spread who receive radiotherapy (RT) to at least one metastatic lesion during routine care. The registry combines information from existing medical records with information collected prospectively. Treating clinical teams choose radiotherapy, imaging, systemic treatment, and follow-up. The registry does not assign treatment or require additional imaging or visits. The classical cohort includes people with 1 to 5 active metastatic lesions assessed by computed tomography (CT) or magnetic resonance imaging (MRI), with or without positron emission tomography (PET). An extended, exploratory cohort includes people with 6 to 10 active metastatic lesions assessed by qualifying fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) or magnetic resonance imaging (MRI). Eligible cancers include cervical, endometrial and other uterine cancers, uterine sarcomas, ovarian and fallopian tube cancers, primary peritoneal cancers, vulvar and vaginal cancers, and other eligible rare gynecologic cancers. The main objective is to describe the time from the first qualifying radiotherapy session or brachytherapy application until imaging shows cancer progression at any site or the participant dies. Other objectives include describing the control of treated lesions, patterns of cancer progression, survival, side effects, subsequent treatment of metastases, and how radiotherapy relates to the continuation or change of systemic treatment. The initial target is 500 participants, with possible expansion to at least 1,000. Follow-up is planned for up to five years using information available from routine care.