Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Esophageal Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

For Cycles 1 and 2, participants received AMG 910 as a short-term intravenous (IV) infusion (approximately 60 minutes) at a dose of 6.5 μg twice a week on Days 1 and 3 of each week in a 28-day cycle. For Cycles 3 to 6, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 6.5 μg weekly, ie, Days 1, 8, 15 and 22 in a 28-day cycle.

For Cycle 1 Week 1, participants received AMG 910 as an extended IV (eIV) infusion (approximately 96 hours) at a dose of 6.5 μg. For the remainder of Cycles 1 and 2, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 6.5 μg twice a week on Days 1 and 3 of each week in a 28-day cycle. For Cycles 3 to 6, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 6.5 μg weekly, ie, Days 1, 8, 15 and 22 in a 28-day cycle.

For Cycle 1 Week 1, participants received AMG 910 as an eIV infusion (approximately 96 hours) at a dose of 15 μg. For the remainder of Cycles 1 and 2, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 15 μg twice a week on Days 1 and 3 of each week in a 28-day cycle. For Cycles 3 to 6, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 15 μg weekly, ie, Days 1, 8, 15 and 22 in a 28-day cycle.

AMG 910

To evaluate the safety and tolerability of AMG 910 in adult subjects, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)

Study of AMG 910 in Subjects With CLDN18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma

A Global Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of the Half-life Extended Bispecific T-cell Engager AMG 910 in Subjects With Claudin 18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

All DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs were defined as any AEs at least possibly related to AMG 910 with an onset within the first 28 days following first dose with any of the following:

* Grade 2 gastric perforation or fistula
* Grade ≥ 3 non-hematologic AEs including laboratory abnormalities
* Re-challenge with AMG 910 after treatment interruption due to any stomach toxicity results in at least same stomach toxicity and is of CTCAE grade ≥ 3 or grade 2 and ongoing for more than 3 days despite optimal supportive treatment
* Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding
* Grade 4 neutropenia lasting \> 28 days
* Febrile neutropenia of any grade
* Anemia requiring transfusion per local or international guidelines in the absence of bleeding
* Grade 5 toxicity
* Any other toxicity related to AMG 910 considered significant enough to be qualified as DLT in the opinion of the investigator

A TEAE was defined as any adverse event starting on or after the first administration of investigational product, as determined by the flag indicating if the adverse event started prior to the first dose on the Events case report form, and up to and including 30 days after the last investigational product dose date.

Evaluation of TEAEs included the number of participants with at least 1 TEAE or treatment-related TEAE. Clinically significant changes in vital signs, electrocardiogram (ECG) and clinical laboratory tests were recorded as TEAEs.

Mean Cmax values for the dosing intervals following short-term IV infusion (Cohort 1) and following extended IV infusions (Cohorts 1b and 2b) for Cycle 1 Week 1, and for short-term IV infusions in subsequent dosing intervals in Cycle 1. The timing of the pharmacokinetic (PK) sampling for Week 1 (Days 1 - 7) was based on hours after the start of the infusion and from Day 8 onwards was based on hours after the end of infusion (EOI). Due to the limited number of samples obtained and early termination of the study, PK data are summarized for Cycle 1 only.

Mean Ctrough values for the dosing intervals following short-term IV infusion (Cohort 1) and following extended IV infusions (Cohorts 1b and 2b) for Cycle 1 Week 1, and for short-term IV infusions in subsequent dosing intervals in Cycle 1 are presented. The timing of the PK sampling for Week 1 (Days 1-7) was based on hours after the start of infusion and from Day 8 onwards was based on hours after EOI. Due to the limited number of samples obtained and early termination of the study, PK data are summarized for Cycle 1 only.

The timing of the PK sampling for Week 1 (Days 1-7) was based on hours after the start of infusion, and for Day 8 after EOI.

Calculated as AR = Cycle 1 Day 22 pre-infusion concentration/Cycle 1 Day 8 pre-infusion concentration.

Mean t1/2 values for the dosing intervals following short-term IV infusion (Cohort 1) and following extended IV infusions (Cohorts 1b and 2b) for Cycle 1 Week 1, and for short-term IV infusions in subsequent dosing intervals in Cycle 1 are presented. The timing of the PK sampling for Week 1 (Days 1-7) was based on hours after the start of infusion and from Day 8 onwards was based on hours after EOI. Due to the limited number of samples obtained and early termination of the study, PK data are summarized for Cycle 1 only.

OR was defined as a best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST v1.1:

* CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \< 10 mm.
* PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Non target lesions must be non-progressive Disease (non-PD).

ORR was defined as the incidence of a BOR of immune complete response (iCR) or immune partial response (iPR) per iRECIST:

* iCR: Disappearance of all non-nodal target and non-target lesions and normalization of pathological lymph nodes (whether target or non-target) to \<10 mm in short axis.
* iPR: At least a 30% decrease in the sum of measures of target lesions, taking as reference the baseline target lesion sum.

Data was not collected due to early termination of study, therefore data are not available.

As no participants experienced an objective response, data were not available.

Data was not collected due to early termination of study, therefore data are not available.

Data was not collected due to limited follow up time due to study termination, therefore data are not available.

Amgen

For all-cause mortality, time frame is from enrollment through end of study including long term follow-up. For SAE and non-serious AEs, time frame is treatment emergent.

For Cycles 1 and 2, participants received AMG 910 as a short-term intravenous (IV) infusion (approximately 60 minutes) at a dose of 6.5 µg twice a week on Days 1 and 3 of each week in a 28-day cycle. For Cycles 3 to 6, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 6.5 µg weekly, ie, Days 1, 8, 15 and 22 in a 28-day cycle.

Cohort 1: AMG 910 6.5 µg

For Cycle 1 Week 1, participants received AMG 910 as an extended IV (eIV) infusion (approximately 96 hours) at a dose of 6.5 µg. For the remainder of Cycle 1 (from Day 8) and for Cycles 2 to 6, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 6.5 µg weekly, ie, Days 1, 8, 15 and 22 in a 28-day cycle.

Cohort 1b: AMG 910 6.5 µg

For Cycle 1 Week 1, participants received AMG 910 as an eIV infusion (approximately 96 hours) at a dose of 15 µg. For the remainder of Cycle 1 (from Day 8) and for Cycles 2 to 6, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 15 µg weekly, ie, Days 1, 8, 15 and 22 in a 28-day cycle.

Cohort 2b: AMG 910 15 µg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Safety Analysis Set: All participants that were enrolled and received at least 1 dose of AMG 910.

The study was discontinued due to a strategic decision to end clinical development for AMG 910 that was unrelated to safety.

Study Director

Safety Analysis Set: All participants that were enrolled and received at least 1 dose of AMG 910. Only participants who received study treatment (at least 80% of the planned dose for Cycle 1) and remained on study through the DLT assessment window were considered DLT-evaluable.

Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)

TEAEs

Treatment-related TEAEs

Number of Participants Who Experienced a Treatment-emergent AE (TEAE)

Cycle 1 Day 1

Cycle 1 Day 3

Cycle 1 Day 7

Cycle 1 Day 8

Cycle 1 Day 10

Cycle 1 Day 15

Cycle 1 Day 17

Cycle 1 Day 22

Cycle 1 Day 24

PK Analysis Set: Includes all participants who have received at least 1 dose of the AMG 910 and have at least 1 PK sample collected. Participants with data available at each time point are included.

Maximum Serum Concentration (Cmax) of AMG 910

Minimum Serum Concentration (Ctrough) of AMG 910

PK Analysis Set: Includes all participants who have received at least 1 dose of the AMG 910 and have at least 1 PK sample collected. Participants with data available are included.

Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC0_168hr)

PK Analysis Set: Includes all participants who have received at least 1 dose of the AMG 910 and have at least 1 PK sample collected. Participants with data available at both time points are included.

Cohort 1 Only: Accumulation Ratio (AR) of AMG 910

Half-life (t1/2) of AMG 910

RECIST Evaluable Analysis Set: Included all participants that were enrolled and received at least 1 dose of AMG 910 with at least 1 tumor lesion that was measurable in contrast-enhanced computed tomography (CT) as defined by RECIST 1.1 at baseline.

Number of Participants With an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

ORR Per Immune RECIST (iRECIST)

RECIST Evaluable Analysis Set: Included all participants that were enrolled and received at least 1 dose of AMG 910 with at least 1 tumor lesion that was measurable in contrast-enhanced CT as defined by RECIST 1.1 at baseline.

Duration of Response (DOR) Per RECIST 1.1

DOR Per iRECIST

Time to Progression Per RECIST 1.1

Time to Progression Per iRECIST

Progression-free Survival (PFS) Per RECIST 1.1

PFS Per iRECIST

Overall Survival

Overall Study

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Cadonilimab (AK104) in combination with pulocimab (AK109) and paclitaxel, iv, every 3 weeks

Placebo in combination with Paclitaxel, iv, every 3 weeks

cadonilimab

pulocimab

paclitaxel

placebo

Ting Liu

Lin Shen, MD

Xiaotian Zhang, MD

This randomized, multicenter, double-blind, phase 3 study will evaluate the efficacy and safety of the combination of cadonilimab (AK104) and pulocimab (AK109) and paclitaxel compared with paclitaxel in patients with advanced gastric or gastroesophageal junction adenocarcinoma who failed first-line immunochemotherapy.

A Study of AK104/Placebo Plus AK109/Placebo And Paclitaxel in Gastric or Gastroesophageal Junction Adenocarcinoma

A Randomized, Double-blind, Phase 3 Study Of Cadonilimab (AK104) Plus Pulocimab (AK109) And Paclitaxel Versus Paclitaxel In Patients With Advanced Gastric Or Gastroesophageal Junction Adenocarcinoma Who Failed First-line Immunochemotherapy

PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first (based on RECIST 1.1 criteria).

OS is defined as the time from randomization to death due to any cause.

ORR is defined as proportion of subjects who have a complete or partial response relative to baseline according to RECIST 1.1 criteria

DoR is defined as the duration from the first documentation of objective response to the first documented disease progression(based on RECIST v1.1 criteria) or death due to any cause, whichever occurs first.

DCR is defined as the proportion of subjects with CR, PR, or SD (based on RECIST v1.1 criteria).

Akeso

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Docetaxel

Afuresertib in combination with Sintilimab and Nab-paclitaxel in patients with Endometrial Cancer and Cervical Cancer

Afuresertib in combination with Sintilimab and Docetaxel in patients with Gastric and Gastroesophageal Junction Adenocarcinoma, Non-Small Cell Lung Cancer and Esophageal Cancer

Afuresertib 125 mg PO on days 1-5, 8-12, 15-19 or Afuresertib 125 mg QD

Afuresertib

Nab-paclitaxel 80 mg/M2 IV D1,8, Q3W or 100 mg/M2 IV D1,8, Q3W

Nab paclitaxel

Docetaxel 50 mg/M2 IV D1 Q3W or Docetaxel 60 mg/M2 IV D1 Q3W

Sintilimab

Shimei Liu

Li Qiu

Lin Shen

Lin Shen, Dr.

Yongsheng Li

Ying Cheng

Tianshu Liu

Rutie Yin

Lin Shen, Director

This is a multicenter, open-label, dose-escalation and efficacy/safety Phase I/II study to assess RP2D, safety, tolerability and anti-tumor activity of Sintilimab + afuresertib + nab-paclitaxel or docetaxel administered as a combination therapy.

This study is designed to identify the MTD and recommended Phase II dose (RP2D) of afuresertib in combination with sintilimab and nab-paclitaxel or docetaxel, respectively, to characterize the PK profile of afuresertib in phase I and to evaluate clinical efficacy and safety of the combination therapy in phase II. The study population in phase II is the patients with one of the five selected cancers who resistant to the prior anti-PD-1/PL-1 treatments (as a monotherapy or in combination with other anti-cancer drugs including chemotherapy) , such as EC, GC/GEJC, EsC, CC, and NSCLC.

This is a multicenter, open-label, dose-escalation and efficacy/safety Phase I/II study to assess RP2D, safety, tolerability and anti-tumor activity of Sintilimab + afuresertib + nab-paclitaxel or docetaxel administered as a combination therapy. This study is designed to identify the MTD and recommended Phase II dose (RP2D) of afuresertib in combination with sintilimab and nab-paclitaxel or docetaxel, respectively, to characterize the PK profile of afuresertib in phase I and to evaluate clinical efficacy and safety of the combination therapy in phase II. The study population in phase II is the patients with one of the five selected cancers who resistant to the prior anti-PD-1/PL-1 treatments (as a monotherapy or in combination with other anti-cancer drugs including chemotherapy) , such as EC, GC/GEJC, EsC, CC, and NSCLC.

For phase I, the MTD is defined as the combination dose level with a DLT rate that is closest to the target toxicity rate (0.3). Patients in each dose level are planned to be enrolled in each cohort of size 3 and maximum to 9. Totally there would be no more than 42 cases in 2 combination groups (maximum 21 patients for each combination group). RP2D evaluation will be based on the observed safety profiles,PK ，PK was analyzed on 3-9 patients per dose of albumin-paclitaxel and docetaxel (pk Sample collection may be less than 3 if the group was discontinued due to DLT observed) . The dose escalation decision will be made based on the observed safety profiles of the tested combined doses and reviewed by the safety committee. The recommended combined dose level will be as follows based on BOIN dose escalation design.

Once the RP2D of Sintilimab + afuresertib + nab-paclitaxel or docetaxel has been established, a cohort consisting of 50-125 patients with stratifying for each cancer type (10 -25 patients for each cancer type) who resistant to anti-PD-1/PD-L1 or its combination therapy (except for CC and EC, who did not receive prior anti-PD-1/PD-L1 could be enrolled.

The preliminary anti-tumor efficacy of Sintilimab + afuresertib + nab-paclitaxel or docetaxel therapy will be assessed by the measurement of ORR, PFS, OS, DOR, DCR based on the tumor assessment in each of the five solid tumors. Patients with biomarkers, such as PTEN/PI3K/AKT alternations, will be analysed retrospectively as the subpopulations for their anti-tumor efficacy in each cancer type.

Afuresertib +Sintilimab+Chemotherapy in Patients With Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1

A Phase I/II Dose-Escalation and Efficacy/Safety Study of Afuresertib Plus Sintilimab Plus Chemotherapy in Patients With Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1 Treatment

Phase I: Findings on physical examination, ECG, vital signs, and reports of the laboratory results based on the CTCAE v5.0

Phase I: Determining the RP2D of the Combination therapy for phase II

Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel in EC/CC/ GC/GEJC/EsC/NSCLC

Phase I: Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel

Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel

Calculated from plasma concentrations of afuresertib obtained at various time points

Phase II: Anti-tumor activity of Afuresertib in combination with Sintilimab and Nab-paclitaxel or Docetaxel in EC/CC/ GC/GEJC/EsC/NSCLC

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of AMG 910 in Subjects With CLDN18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma	NCT04260191	Gastric and Gas...	AMG 910	18 Years - 99 Years	Amgen
A Study of AK104/Placebo Plus AK109/Placebo And Paclitaxel in Gastric or Gastroesophageal Junction Adenocarcinoma	NCT06341335	Gastric and Gas...	cadonilimab pulocimab paclitaxel placebo	18 Years - 75 Years	Akeso
Afuresertib +Sintilimab+Chemotherapy in Patients With Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1	NCT05383482	Solid Tumor NSCLC Cervical Cancer Endometrial Can... Esophageal Canc... Gastric and Gas...	Afuresertib Nab paclitaxel Docetaxel Sintilimab	18 Years -	Laekna Limited

Spots Global Cancer Trial Database for gastric and gastroesophageal junction adenocarcinoma