Clinical Research Directory

AACR Adaptive Biomarker-Driven Organ Preservation Trial in Gastroesophageal Adenocarcinomas

This study will test a new personalized treatment approach for patients with stomach or esophageal cancer. It will take place in two stages and aims to find the best combination of chemotherapy, immunotherapy, and targeted drugs based on each patient's tumor biomarkers. Upon enrollment onto the study, patients will consent to tumor biomarker testing and may receive one cycle of standard chemotherapy while awaiting results. Those with a matching biomarker will join the corresponding treatment group that combines chemotherapy, an immune checkpoint inhibitor, and/or a targeted therapy. In Stage I of the study, treatment lasts about four months before surgery, followed by an additional eight months of therapy for a total of one year. The most effective treatments from Stage I will be studied further in Stage II of the study to see whether some patients can safely avoid surgery. Those patients enrolled during Stage II will receive four months of the same combination treatment (chemotherapy, an immune checkpoint inhibitor, and/or a targeted therapy) but may be eligible to skip surgery if their cancer completely disappears after pre-surgery therapy. All patients will then receive an additional eight months of therapy and those who skipped surgery will be closely monitored with scans and endoscopies.

Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06)

This is a phase 1/2 multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of sacituzumab tirumotecan (MK-2870) plus paclitaxel versus ramucirumab plus paclitaxel, and HER3-DXD plus ramucirumab versus ramucirumab plus paclitaxel for the treatment of participants with advanced or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, or esophageal adenocarcinoma who have failed 1 prior line of therapy. This is an estimation study, and no formal hypothesis testing will be performed.

Substudy 06C: A Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06)

This is a phase 1/2, multicenter, open-label umbrella platform study that will evaluate the safety and tolerability of investigational agents with pembrolizumab and fluoropyrimidine chemotherapy for the first-line (1L) treatment of participants with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for investigational agents in combination with chemotherapy and immunotherapy. There is no formal hypothesis in this study.

A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers

This study is being done to find out if zanidatamab, when given with chemotherapy plus or minus tislelizumab, is safe and works better than trastuzumab given with chemotherapy. The patients in this study will have advanced human epidermal growth factor 2 (HER2)-positive stomach and esophageal cancers that are no longer treatable with surgery (unresectable) or chemoradiation, and/or have grown or spread to other parts of the body (metastatic).

A Study of Novel Agents or Combinations as Perioperative Treatment in Participants With Locally Advanced Resectable Gastroesophageal Adenocarcinoma

GEMINI-PeriOp GC study will assess the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of novel agents or novel combinations as perioperative treatment in participants with locally advanced resectable gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma who have not received previous treatment for the disease.

Response Adapted Neoadjuvant Therapy in Gastroesophageal Cancers (RANT-GC Trial)

This is a phase 1b prospective, single arm, open-label trial determining the efficacy and feasibility of using a response-guided approach to help guide neoadjuvant chemotherapy in subjects with Stage IB, II or Stage III adenocarcinoma of the stomach or gastroesophageal junction (GEA).

Trial Comparing Standard of Care Therapy With and Without Sequential Cytoreductive Intervention for Patients With Metastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid (ctDNA) Levels

This is a randomized, open label, single-center, phase 2, randomized controlled trial of sequential cytoreductive intervention versus standard of care therapy for patients with intervenable oligometastatic (stage IV) cancer of the upper gastrointestinal (GI) tract and undetectable ctDNA at the time of randomization after a three-month induction chemotherapy period.

Zanidatamab in Combination With Pembrolizumab and Chemotherapy in HER2 and PD-L1 Positive Metastatic Gastroesophageal Adenocarcinoma (GEA) Patients

The ZANGEA trial is a open-label, single arm, multicenter phase II trial assessing the efficacy of zanidatamab in combination with pembrolizumab and chemotherapy in patients with metastatic gastroesophageal adenocarcinoma (GEA). The patients need to be previously untreated in the palliative setting and tested positive for HER2 and PD-L1.

Paclitaxel and Ramucirumab +/- Zanidatamab in HER2 Postive Advanced Gastroesophageal Adenocarcinoma

This study is being done to answer the following question: Can the chance of gastroesophageal cancer growing or spreading be lowered by adding a drug called zanidatamab to the usual combination of drugs? We are doing this study because we want to find out if this approach is better or worse than the usual approach for this type of cancer. The usual approach is defined as care most people get for gastroesophageal cancer

Adebrelimab Combined With Induction Chemotherapy or SHR-8068 for Mismatch Repair-Deficient/Microsatellite Instability-High (dMMR/MSI-H) Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma：A Randomized, Non-comparative Phase 2 Study

This is a randomized, non-comparative, open-label, two-arm phase II clinical trial designed to evaluate the efficacy and safety of neoadjuvant therapy with adebrelimab plus induction chemotherapy versus adebrelimab plus SHR-8086 in patients with dMMR/MSI-H gastric or gastroesophageal junction adenocarcinoma.

A First-in-Human Study Using BDC-4182 as a Single Agent in Advanced Gastric and Gastroesophageal Cancer

A first-in-human study using BDC-4182 as a single agent in gastric and gastroesophageal cancers

Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease

This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine strategy in patients with solid tumors and molecular residual disease. The hypothesis of the trial is that synthetic long peptide personalized cancer vaccines will be safe and capable of generating measurable neoantigen-specific T-cell responses enabling ctDNA clearance. The personalized cancer vaccines are composed of synthetic long peptides corresponding to prioritized cancer neoantigens and will be co-administered with poly-ICLC.

Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Advanced Solid Tumors Receiving Intravenous (IV) ABBV-400 as Monotherapy and in Combination With IV Bevacizumab

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess adverse events and change in disease activity when ABBV-400 is given to adult participants to treat advanced solid tumors. ABBV-400 is an investigational drug being developed for the treatment of advanced solid tumors. Study doctors put the participants in groups called treatment arms. The Recommended Phase 2 dose (RP2D) will be explored. Each treatment arm receives a different dose of ABBV-400. This study will include a dose escalation phase to determine the best dose of ABBV-400, followed by a dose expansion phase to confirm the dose and combination with bevacizumab. Approximately 500 adult participants with NSCLC, gastroesophageal adenocarcinoma/gastroesophagel junction adenocarcinoma (GEA) and colorectal cancer (CRC) or advanced solid tumors, will be enrolled in the study in approximately 7-10 sites in the Dose Escalation phase and 85-95 sites in the Dose Expansion phase worldwide. Dose escalation arms, participants will receive intravenous (IV) escalating doses of ABBV-400 monotherapy. Dose expansion arms, participants in the following advanced solid tumor indications: non-squamous NSCLC with wildtype EGFR-expression (wtEGFR NSCLC) \[Part 2i\] or mutated EGFR-expression (mutEGFR NSCLC) \[Part 2ii\], squamous NSCLC \[Part 2iii\], GEA \[Part 3\] will receive intravenous (IV) ABBV-400 monotherapy, participants CRC will receive IV ABBV-400 monotherapy in expansion \[Part 4\], participants MET amplification will receive IV ABBV-400 monotherapy in expansion \[Part 5\], participants MET mutation will receive IV ABBV-400 monotherapy in expansion \[Part 6\], participants CRC safety lead in will receive escalating doses of IV ABBV-400 in combination with IV bevacizumab \[Part 7a\], and participants CRC dose optimization in will the low or high dose of IV ABBV-400 determined in Part 7a in combination with IV bevacizumab or oral trifluridine/tipiracil (TAS-102) tablets \[Part 7b\]. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

A Clinical Trial Evaluating TQB2102 for Injection in Combination With Behmosubaisumab/Payamprolizumab With or Without Chemotherapy in Unresectable Locally Advanced, Recurrent, or Metastatic Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastroesophageal Adenocarcinoma

TQB2102 for injection is a novel antibody-coupled drug (ADC) that enhances binding to tumor cell surface HER2 proteins by simultaneously targeting the two non-overlapping epitopes of the HER2 protein, Endothelial Cell Dysfunction 2 (ECD2) and Endothelial Cell Dysfunction 4 (ECD4), increasing HER2 internalization, and then down-regulating the tumor cell surface HER2 proteins more effectively, and doubly blocking the HER2 signaling, to achieve the effects of trastuzumab and Pertuzumab alone and in combination. This is a Phase II study to evaluate the efficacy and safety of TQB2102 for injection in combination with Benmelstobart Injection /Penpulimab Injection ± chemotherapy in patients with unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma

Phase II Study of Short Course FOLFOX Chemotherapy With Either Nivolumab or Nivolumab + Radiation in the First Line Treatment of Metastatic or Unresectable Gastroesophageal Cancers (BMS Protocol CA209-76L)

This is a randomized phase II study examining nivolumab alone versus radiation therapy with nivolumab in subjects who did not have disease progression to initial therapy with the combination of FOLFOX and Nivolumab.

Adebrelimab With Chemoradiotherapy and Surgery for G/GEJ

Gastric cancer is one of the most common and deadly cancers globally, characterized by a poor prognosis. Approximately 70% of patients are diagnosed at an advanced stage, and the 5-year survival rate is only around 10%. While advancements in targeted therapies and immunotherapy have improved treatment efficacy and extended survival, advanced gastric and gastroesophageal junction adenocarcinomas remain incurable. Subgroup analyses indicate that patients with limited metastases, such as liver oligometastasis or retroperitoneal lymph node metastasis, may benefit more from conversion therapy. However, current guidelines do not recommend specific treatment protocols for gastric cancer with limited metastasis. Immunotherapy has shown moderate efficacy in selected patients with advanced gastric adenocarcinoma. Additionally, low-dose radiotherapy (LDRT) may synergistically enhance antitumor responses when combined with immunotherapy. This Phase II trial aims to evaluate the safety and efficacy of combining Adebrelimab, chemotherapy, and LDRT before surgery in treating adult patients with gastric or gastroesophageal junction adenocarcinoma.

The Sequential Combination of FOLFOX and Toripalimab for Perioperative Immuno-Oncology Therapy of HER2-negative Adenocarcinoma of the Esophagogastric Junction (Siewert I/II):

The addition of immunotherapy to chemotherapy improves outcomes in patients with HER2-negative gastroesophageal adenocarcinoma (GEA), and investigators aim to explore its role in the perioperative setting. Moreover, optimizing the timing schedule of these two therapies is critical when balancing efficacy and safety. This Chinese, multicenter, open-label phase 1b/2 trial will evaluate the efficacy and toxicity of perioperative folinic acid, fluoro-uracil, oxali-platin (FOLFOX), and toripalimab (JS001, a novel PD-1 inhibitor) in combination at various schedules in the neoadjuvant setting in patients with HER2-negative resectable GEA: three cycles each in Arm A: FOLFOX (D1, q2w) followed by toripalimab (D3, 3 mg/kg, q2w); Arm B: concurrent FOLFOX (D1, q2w) combined with toripalimab (D1, 3 mg/kg, q2w); Arm C: toripalimab (D1, 3 mg/kg, q2w) followed by FOLFOX (D3, q2w); Arm D: FOLFOX (D1, q2w) alone. The primary end-point is the dose-limiting toxicity in Phase 1b and the pathological complete response rate in Phase 2; secondary end-points include major pathologic response, disease-free survival, and event-free survival.A fixed sample size of 126 patients is used in this study, with a safety run-in period (n = 6) and cohort expansion period (n = 24), a dropout rate of 5% within 12 months of follow-up. Each arm receives three cycles of FOLFOX (D1, q2w) followed by 15 cycles of toripalimab (D1, 240 mg, q3w) in the neoadjuvant setting. Pre-treatment biopsies, post-resection specimens, serial liquid biopsy, and gut microbiota samples on treatment will be collected to explore the biomarkers' predictive value on diverse schedule efficacy and safety.