Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Stomach Cancer

Pancreatic Cancer

A dose escalation design will be used to determine the Maximum Tolerated Dose (MTD) and/ or the Recommended Phase 2 Dose (RP2D) regimens to be further evaluated in the Dose Expansion arms.

Dose escalation part consists of six parts (Part A, B, C, D, E, and F), and up to 75 patients would be enrolled in total. Participants will be assigned to sequentially escalating dose cohorts of ASP2138 in each part. The study will open with the Part A dosing schedule, while subsequent cohorts will be opened sequentially or in parallel based upon sponsor review of emerging data.

Participants will receive ASP2138 at the RP2D regimens determined in Dose Escalation arm.

ASP2138

Astellas Pharma Global Development, Inc.

Senior Director

Claudin 18.2 protein, or CLDN18.2 is a protein found on cells in the digestive system. It is also found on some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to 2 targets at the same time: CLDN18.2 and a protein called CD3 found on immune cells, called T-cells. ASP2138 works by binding to both the tumor cell and CD3 which "tells" the immune system to attack the tumor.

ASP2138 is a potential new treatment for people with stomach cancer, gastroesophageal junction cancer, (cancer where the tube that carries food (esophagus) joins the stomach) or pancreatic cancer. Before ASP2138 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. This information will help to find a suitable dose and to check for potential medical problems from the treatment.

Adults 18 years or older with stomach cancer, gastroesophageal junction cancer, or pancreatic cancer can take part. Their cancer is locally advanced unresectable or metastatic. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body.

The main aims of the study are to check the safety of ASP2138, how well it is tolerated, and to find a suitable dose of ASP2138 to be used later in this study.

This is an open-label study. This means that people who take part in this study and clinic staff will know that people will receive ASP2138.

The study will have 2 phases. In phase 1, different small groups of people will receive lower to higher doses of ASP2138. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP2138 to use later in the study. The first group will receive the lowest dose of ASP2138. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP2138. The panel will do this for each group until all groups have received ASP2138, or until suitable doses have been selected for later in the study. Doctors will also check how each type of cancer is responding to ASP2138.

In phase 1b, other different small groups will receive suitable doses of ASP2138 found from phase 1. Phase 1b will check how each type of cancer responds to ASP2138. The response to ASP2138 is measured using scans and blood tests. Doctors will continue to check for all medical problems throughout the study.

ASP2138 will be given either through a vein in the arm (intravenous infusion) or just below the skin (subcutaneous injection). Treatment will be in cycles of either 7 or 14 days (1 or 2 weeks). In each treatment cycle, intravenous infusions or subcutaneous injections will either be given once a week or once every 2 weeks.

People will continue to receive treatment until: their cancer gets worse; they have medical problems they can't tolerate; they ask to stop treatment; the doctors decide that continuing treatment is no longer in that person's best interest; the study is ended by the sponsor. Doctors will check if people had any medical problems from ASP2138. Other checks will include medical examinations, checking the nervous system, blood and urine tests and vital signs. Nervous system checks include checking peoples state of mind, reflexes, balance, movement and muscle strength. Vital signs include medical examinations, body temperature, breathing rate, and blood oxygen levels. Electrocardiograms (ECG) will be done to check the heart rhythm during the study. People will receive ASP2138 in a hospital. They will have blood tests and doctors will check for medical problems. People will also visit the clinic on certain days during their treatment, with extra visits during the first 3 cycles of treatment.

People will visit the clinic after treatment has finished. The doctors will check for more medical problems. Other checks will include medical examinations, blood and urine tests, and vital signs. People will also have an ECG and may have CT or MRI scans.

After this, people will visit the clinic for a check-up several times. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not.

A Study of ASP2138 in Adults With Stomach Cancer, Gastroesophageal Junction Cancer, Pancreatic Cancer

A Phase 1/1b Study of ASP2138 in Participants With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma or Metastatic Pancreatic Adenocarcinoma Whose Tumors Have Claudin (CLDN) 18.2 Expression

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

A DLT is defined as any of the prespecified Adverse Events (AEs) (graded using National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 5.0, except cytokine release syndrome \[CRS\] and immune effector cell-associated neurotoxicity syndrome \[ICANS\] which are graded using American Society for Transplantation and Cellular Therapy \[ASTCT\] consensus grading) or laboratory findings that the investigator or sponsor cannot clearly attribute to a cause other than study drug occurring during the DLT evaluation period.

An AE is any untoward medical occurrence temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator and events related to the (study) procedures.

An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or other medically important events.

Number of participants with potentially clinically significant laboratory values.

Number of participants with potentially clinically significant vital sign values.

Number of participants with potentially clinically significant ECG values.

Number of participants with potentially clinically significant physical exam values.

The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.

AUCtau will be recorded from the PK serum samples collected.

Cmax will be recorded from the PK serum samples collected.

Ctrough will be recorded from the PK serum samples collected.

Tmax will be recorded from the PK serum samples collected.

ORR is defined as the proportion of participants for each dosing scheme whose best overall response is rated as confirmed complete response (CR) or partial response (PR) per RECIST 1.1.

DCR is defined as the proportion of participants for each dosing scheme whose best overall response is rated as confirmed CR, PR or stable disease (SD) per RECIST 1.1.

Serum CA19-9 level will be assessed by local laboratory in participants with pancreatic cancer.

Comparison of CLDN18.2 expression in baseline versus on-treatment tumor biopsies will be performed.

Comparison of PD-L1 expression in baseline versus on-treatment tumor biopsies will be performed.

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Oxaliplatin

Antimetabolites

According to "3+3" design, a dose of Q-1802 with two dose groups from low to high and one cycle fixed-dose XELOX will be given in DLT observation period. After DLT observation period, Q-1802+XELOX will be given by investigator,s decision until the subject meets study treatment discontinuation criteria.

Phase II:Participants will be randomized to group A and B. Group A:receive a dose of Q-1802 at Cycle 1 Day 1 followed by a same dose in subsequent cycles every 2 weeks. Additionally, participants will receive XELOX (capecitabine/oxaliplatin) treatment until investigator confirmed disease progression or a total of 8 treatments (each cycle is defined as approximately 21 days). Oxaliplatin is administered on day 1 of each cycle, whereas capecitabine is taken twice daily on days 1 through 14. After a maximum of 8 treatments of Oxaplatin, subjects may continue to receive Q-1802 a every 2 weeks each cycle and capecitabine every 3 weeks at the investigator's discretion until the subject meets study treatment discontinuation criteria. Group B:Participants will receive XELOX (capecitabine/oxaliplatin) treatment alone until a total of 8 treatments (each cycle is defined as approximately 21 days). subjects may continue to receive capecitabine every 3 weeks at the investigator's discretion.

Q-1802：A dose Q-1802 will be administered intravenously Q2W. XELOX（oxaliplatin，capecitabin）: 21 days as a cycle Oxaliplatin will be administered 130mg/m2 as a 2-hour IV infusion,administer once on the first day, with 21 days as a cycle Capecitabine will be administered 1000mg/m2 orally twice daily (D1-D14),21ds is one cycle.

Q-1802 Injection,Oxaliplatin Injection,Capecitabine

LI WEI, MD

Lin Shen, MD

The main purpose of this study is to evaluate safety, tolerability and the efficacy of Q-1802 plus SOC compared with SOC. .Pharmacokinetics (PK) ,Pharmacodynamics (PD) of Q-1802 and the immunogenicity profile of Q-1802 will be evaluated as well.

This study is a multicenter, open label, phase Ⅰb/Ⅱ clinical study conducted in unresectable patients with advanced or recurrent metastatic Claudin18.2 positive (medium and high expression) and HER-2 negative primary gastric adenocarcinoma or gastric esophageal junction adenocarcinoma. The Phase Ib dose escalation study included two dose groups each combined with the XELOX standard treatment regimen. Perform dose escalation to obtain MTD and/or RP2D doses for combined administration. The Phase II study adopted an open label parallel randomized controlled design. Further observe the efficacy and safety of Q-1802 combined with XELOX regimen in treating patients with moderate to high expression of Claudin 18.2, and compare and analyze the efficacy and safety of Q-1802 combined with XELOX regimen and XELOX regimen alone.

Phase Ib: Dose escalation;Phase II:Arm A：Combined administration group Q-1802 plus XELOX,Arm B Standard treatment group: XELOX alone

The Safety and Efficacy of Q-1802 Combined With XELOX in Gastrointestinal Tumors

A Phase I/II Clinical Trial to Evaluate the Safety Tolerance and Initial Efficacy of Q-1802 Combined With Standard Treatment in Patients With Gastrointestinal Tumors

TRAE is defined as the AEs that the casual relationship of the AE is ralated to Q-1802

ORR is defined as proportion of participants with complete response, partial response (CR+PR).

PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression or death which occurs first.

QureBio Ltd.

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Analgesics

Pembrolizumab

Antibodies

Immunomodulating Agents

Immunoglobulins

Interleukin-2

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Administered via SC injection once every 7 days or once every 21 days at escalating doses

ALKS 4230 will be administered via SC injection once every 7 or 21 days at escalating doses or at the recommended phase 2 dose and schedule; pembrolizumab will be administered as an intravenous infusion given over 30 minutes; the dose level for pembrolizumab will be 200 mg per the approved label. In December 2020, an RP2D of 3 mg with an administration schedule of q7d was determined for SC ALKS 4230.

SC injection administered in the back of the arm or the abdomen

ALKS 4230

Administered as an intravenous (IV) infusion over 30 minutes

Mural Oncology Medical Director

This study will characterize the safety and tolerability and identify the recommended Phase 2 dose (RP2D) of subcutaneous (SC) ALKS 4230 as monotherapy and in combination with pembrolizumab.

This study will evaluate ALKS 4230 administered SC as lead-in monotherapy and in combination with pembrolizumab in subjects with advanced solid tumors.

A Dose Escalation and Cohort Expansion Study of Subcutaneously-Administered Cytokine ALKS 4230 (Nemvaleukin Alfa) as a Single Agent and in Combination With Anti-PD-1 Antibody (Pembrolizumab) in Subjects With Select Advanced or Metastatic Solid Tumors (ARTISTRY-2)

A Phase 1/2 Study of ALKS 4230 Administered Subcutaneously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors - ARTISTRY-2 (001)

At this time, IPD sharing has not been defined and/or decided if it will be shared.

Includes AEs that are both serious and drug-related

Overall Response rate (ORR) will be based on investigator review of radiographic and photographic images

Overall response rate (ORR) will be based on investigator review of radiographic or photographic images

ORR will be based on investigator review of radiographic or photographic images

Time from first dose of SC ALKS 4230 to the time of progression or death

Time from first dose of SC ALKS 4230 to the time of death

Concentration vs time and standard pharmacokinetic (PK) parameters will be summarized by dose level

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of ASP2138 in Adults With Stomach Cancer, Gastroesophageal Junction Cancer, Pancreatic Cancer	NCT05365581	Gastric Adenoca... Gastroesophagea... Pancreatic Aden...	ASP2138	18 Years -	Astellas Pharma Inc
The Safety and Efficacy of Q-1802 Combined With XELOX in Gastrointestinal Tumors	NCT05964543	Gastroesophagea...	Q-1802 Injectio...	18 Years - 75 Years	QureBio Ltd.
A Dose Escalation and Cohort Expansion Study of Subcutaneously-Administered Cytokine ALKS 4230 (Nemvaleukin Alfa) as a Single Agent and in Combination With Anti-PD-1 Antibody (Pembrolizumab) in Subjects With Select Advanced or Metastatic Solid Tumors (ARTISTRY-2)	NCT03861793	Advanced Solid ...	ALKS 4230 Pembrolizumab	18 Years -	Mural Oncology, Inc

Spots Global Cancer Trial Database for gastroesophageal junction (gej) adenocarcinoma