Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Rare Diseases

Recurrence

Esophageal Neoplasms

Carcinoma

Adenocarcinoma

Stomach Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Stomach Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Olaparib

Immunoglobulins

Ramucirumab

Lexatumumab

Poly(ADP-ribose) Polymerase Inhibitors

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive olaparib PO BID on days 1-14 of each cycle and ramucirumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Michael Cecchini

This phase I/II trial studies the side effects and best dose of olaparib when given together with ramucirumab and how well they work in treating patients with gastric or gastroesophageal junction cancer that has spread to other places in the body (metastatic), has come back (recurrent), or cannot be removed by surgery (unresectable). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as ramucirumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving olaparib and ramucirumab may work better in treating patients with gastric or gastroesophageal junction cancer compared to ramucirumab and paclitaxel (a chemotherapy drug) or ramucirumab alone.

PRIMARY OBJECTIVES:

I. To determine the safe dose of olaparib with ramucirumab, but not to exceed olaparib dose of 300 mg twice daily (tablet formulation). (Phase I) II. To determine the efficacy of olaparib plus ramucirumab as measured by the objective response rates (ORR) stratified by BROCA-HR biomarker status. (Phase II).

SECONDARY OBJECTIVES:

I. To estimate median progression-free survival (PFS) stratified by BROCA-HR biomarker status.

II. To estimate median overall survival (OS) stratified by BROCA-HR biomarker status.

III. To measure the prevalence of the BROCA-HR biomarker in our study population.

IV. To determine toxicity of olaparib and ramucirumab combination.

EXPLORATORY OBJECTIVES:

I. To assess the correlation between the signature 3 status, and mutations in BROCA-HR panel.

II. To evaluate the association between findings from BROCA-HR panel with response to therapy.

III. To evaluate the association between findings from BROCA-HR panel and signature 3 results with response to therapy.

IV. To determine results of immunoassay for poly-ADP-ribosylated (PAR) substrates in tumor tissue.

V. To create a PDX model to study deoxyribonucleic acid (DNA) repair in gastric tumors treated with PARP inhibitors (PARPi) from both pre-treatment biopsy and repeat biopsy after 16 weeks of treatment.

VI. Development of a novel genomic assay for BRCAness. VII. Defining T cell receptor diversity of gastric cancer patients +/- BRCAness.

VIII. Biobank additional tumor tissue for future genomic analysis. IX. Biobank peripheral blood for future genomic analysis and assessment of circulating tumor DNA.

OUTLINE: This is a phase I, dose-escalation study of olaparib followed by a phase II study.

Patients receive olaparib orally (PO) twice daily (BID) on days 1-14 of each cycle and ramucirumab intravenously (IV) over 60 minutes on day 1 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 6 weeks thereafter.

Olaparib and Ramucirumab in Treating Patients With Metastatic or Locally Recurrent Gastric or Gastroesophageal Junction Cancer That Cannot Be Removed by Surgery

A Phase 1/2 Study of Olaparib in Combination With Ramucirumab in Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma (10017760)

The association of BROCA HR assay with Signature 3 will be assessed using a series of contingency table analyses. The association of the presence of an individual mutation from the BROCA HR panel with the signature 3 (yes/no) using Fisher's exact test. Using a Cochran Mantel Haenzel test the relationship across all three measures will be examined. Finally, the relationship of each of these measures with response will be examined. To do this multiple logistic regression models can be fit with the response (complete response/partial response vs stable disease/partial disease) considered as the outcome variable and the assay measures can be used predictors.

Will be assessed by National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) for Adverse Events version 5.0.

Will be defined as complete or partial response assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Will be estimated using the 95% confidence interval (CI) based on Wilson's method. A 5% 2-sided alpha will be used. The Wilcoxon rank sum test and Fisher's exact test will be applied to study the association between the response status and the continuous and categorical variables, respectively. The generalized non-linear model and logistic regression will be applied for multivariable data analysis. The adjusted p-value and 95% CI of the odds ratio will be reported.

Will be compared for duration of response survival with Kaplan-Meier estimates and log-rank tests. The Rothman CI will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease of the PFS data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.

Will be compared for duration of response survival with Kaplan-Meier estimates and log-rank tests. The Rothman CI will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.

Will be assessed by NCI CTCAE version 5.0. Will be tabulated by type and grade and compared to established rates for ramucirumab monotherapy. Ninety-five percent confidence intervals will be calculated for each of these.

National Cancer Institute (NCI)

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Squamous Cell

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.

Patients receive cixutumumab IV over 1 hour on days 1 and 15, and paclitaxel as in Arm I.

Cixutumumab

Laboratory Biomarker Analysis

Pharmacological Study

Steven J Cohen

This randomized phase II trial studies how well paclitaxel with or without cixutumumab works in treating patients with esophageal cancer or gastroesophageal junction cancer that has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cixutumumab may kill cancer cells by blocking the action of a protein needed for cancer cell growth. Giving paclitaxel with or without cixutumumab may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone as second-line therapy in patients with metastatic esophagus or gastroesophageal (GE) junction cancer.

SECONDARY OBJECTIVES:

I. To evaluate the overall survival of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone in this patient population.

II. To evaluate the response rate of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone in this patient population.

III. To evaluate the toxicity of cixutumumab (IMC-A12) plus paclitaxel versus paclitaxel alone in this patient population.

IV. Exploratory analyses will assess potentially relevant cixutumumab (IMC-A12) pharmacodynamic biomarkers obtained from serum samples, including but not limited to, insulin-like growth factor (IGF)-I, IGF-II, insulin-like growth factor binding protein (IGFBP)-2, and IGFBP-3.

OUTLINE: Patients are equally randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle.

ARM II: Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle and paclitaxel as in Arm I.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer

Randomized Phase II Study of Paclitaxel With or Without the Anti-IGF-IR mAb Cixutumumab (IMC-A12) as Second Line Treatment for Patients With Metastatic Esophageal or GE Junction Cancer

Progression-free survival (PFS) is defined as the time from randomization to progression or death without evidence of progression. For cases without documentation of progression, follow-up was censored at the date of last disease assessment without progression, unless death occurred within a short period of time (4 months) following the date last known progression-free, in which case the death was counted as an event, or in the case of death within 4 months of randomization in the absence of disease evaluation before that time. PFS was estimated using the Kaplan-Meier method, with 90% confidence intervals calculated using Greenwood's formula, and compared by the log rank test.

Overall survival (OS) is defined as the time from randomization until death (event), or censored at last date known alive. OS was estimated using the Kaplan-Meier method, with 90% confidence intervals calculated using Greenwood's formula, and compared by the log rank test.

Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level. PR is defined as disappearance of target lesions or at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.

Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.

Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle.

paclitaxel: Given IV

Arm I (Paclitaxel)

Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I.

cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight

paclitaxel: Given IV

Arm II (Cixutumumab, Paclitaxel)

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Per protocol, the primary population for all efficacy endpoints is all eligible patients

Study Statistician

Progression-free Survival

Overall Survival

Objective Response Rate

Overall Study

Phase 1: MLN0264 1.2 milligram per kilogram (mg/kg) starting dose, Intravenous (IV), on Day 1 of 3 week cycles, for up to 1 year or until disease progression or unacceptable toxicity. Dosage of MLN0264 will be increased to 1.5 mg/kg then 1.8 mg/kg using a 3 + 3 dose escalation design to determine a maximum tolerated dose (MTD) and/or recommended Phase 2 Dose (RP2D).

Phase 2: MLN0264, IV, on Day 1 of 3 week cycles, for up to 1 year or until disease progression or unacceptable toxicity. Dosage for this phase will be determined from results of Phase 1 MTD/RP2D.

MLN0264

Medical Director Clinical science

The purpose of this study is to evaluate the effects of MLN0264 in previously treated Asian participants with Advanced Gastrointestinal (GI) Carcinoma (Phase 1) or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma (Phase 2) Expressing Guanylyl Cyclase C (GCC).

The drug being tested in this study is called MLN0264. This drug is being evaluated to check the effects on previously treated Asian individuals with Advanced GI Carcinoma (Phase 1) or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma (Phase 2). The study will enroll approximately 95 participants.

In Phase 1, approximately 14 Asian participants with GI malignancies will be enrolled in 3 planned dose cohorts according to the traditional 3 + 3 dose escalation scheme. The starting dose will be 1.2 mg/kg of MLN0264 administered IV on Day 1 of 3-week cycles for up to 1 year or until disease progression or unacceptable toxicity occurs. Dose escalation will take place until Phase 2 recommended dose is determined.

In Phase 2, eligible Asian participants with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction will be enrolled. Participants must have failed at least 2 lines of prior anticancer therapy for advanced or metastatic disease. Disease recurrence within 6 months of the last dose of post-surgical adjuvant chemotherapy counts as 1 line of prior anticancer therapy for advanced disease.

This multi-center trial will be conducted in Japan, Korea and Taiwan. The overall time to participate in this study is up to 3 years.

MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

A Phase 1/2 Trial of MLN0264 in Previously Treated Asian Patients With Advanced Gastrointestinal (GI) Carcinoma (Phase 1) or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma (Phase 2) Expressing Guanylyl Cyclase C (GCC)

Toxicity evaluated as per NationalCancerInstituteCommonTerminologyCriteria for AEs (NCI CTCAE),version 4.03.DLT=any event related to MLN0264:Grade 4 neutropenia(absolute neutrophil count\[ANC\]less than\[\<\]500 cells/millimeter\[mm\]\^3); \>=Grade 3 neutropenia with fever/infection;Grade 4 thrombocytopenia(platelets \<25,000/mm\^3)/requires platelet transfusion(with/without hemorrhage);Grade 3/greater thrombocytopenia with clinically meaningful bleeding;Anemia requiring blood transfusion;\>=Grade 3 nausea/emesis occurring despite using optimal anti-emetic prophylaxis;\>=Grade 3 diarrhea despite optimal supportive care measures;any other \>=Grade 3 nonhematologic toxicity except brief(\<1 week)Grade 3 fatigue;Inability to start next therapy cycle greater than (\>)2 weeks due to delayed treatment and adequate recovery of MLN0264-related hematologic or nonhematologic toxicity;other\>= Grade 2 MLN0264-related nonhematologic toxicity which requires dose reduction or discontinuation of therapy.

The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Laboratory assessment includes serum chemistry, hematology, urine analysis and coagulation.

Vital signs include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (beats per minute \[bpm\]).

RP2D is maximum tolerated dose(MTD) in study Phase1.MTD was highest dose of MLN0264 given at which \<=1 of 6 participants experienced DLTduring Cycle1 of Phase1.DLT=any event related to MLN0264:Grade 4 neutropenia ANC less than\<500 cells mm\^3;\>=Grade 3 neutropenia with fever/infection;Grade 4 thrombocytopenia(platelets \<25,000/mm\^3)/requires platelet transfusion(with/without hemorrhage);Grade 3/greater thrombocytopenia with clinically meaningful bleeding;Anemia requiring blood transfusion;\>=Grade 3 nausea/emesis occurring despite using optimal anti-emetic prophylaxis;\>=Grade 3 diarrhea despite optimal supportive care measures;any other \>=Grade 3 nonhematologic toxicity except brief(\<1 week)Grade 3 fatigue;Inability to start next therapy cycle\>2 weeks due to delayed treatment and adequate recovery of MLN0264-related hematologic or nonhematologic toxicity;other\>= Grade 2 MLN0264-related nonhematologic toxicity which requires dose reduction or discontinuation of therapy.

ORR is the percentage of participants with complete response \[CR\] + partial response \[PR\]) based on modified Response Evaluation Criteria in Solid Tumors (RECIST). Overall response rate (CR + PR) based on modified RECIST version 1.1 guidelines. CR: Disappearance of all target lesions and PR: at least a 30 percentage (%) decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. All measurable lesions up to a maximum of 2 lesions per organ, 5 lesions in total representative of all involved organs were identified as target lesions at baseline. Target lesions were selected on the basis of size (longest lesions) and suitability for reproducible repeated measurements.

Blood samples was collected predose to evaluate ATA. Data was collected only for limited period due to early termination of the study.

Disease response was based on the investigator's assessment using the modified RECIST version 1.1 guidelines. Evaluation of target lesions included CR (Disappearance of all target lesions),PR(at least a 30% decrease in the sum of the LD of target lesions),Progressive disease (PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions) and Stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD).Evaluation of Non target Lesions included CR (disappearance of all non target lesions and normalization of tumor marker level), Incomplete response/SD (Persistence of 1 or more non target lesions and/or maintenance of tumor marker level above the normal limits) and PD(Appearance of 1 or more new lesions and/or unequivocal progression of existing non target lesions).

PFS is defined as the time from the date of first study drug administration to the date of first documentation of progressive disease or death. For a participant who has not progressed and is last known to be alive, PFS was censored at the last response assessment that was stable disease or better. PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions.

DOR is defined as the time from the date of first documentation of a confirmed response to the date of first documentation of Progressive Disease (PD). Responders without documentation of PD were censored at the last response assessment that was stable disease or better. CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD and PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions.

DCR is defined as Complete Response (CR) rate + Partial Response (PR) rate + stable disease (SD) rate with a minimum of 12 weeks' duration. Duration of SD is defined as the time from the date of first study drug administration to the date of first documentation of disease progression for participants who achieved SD as the best overall response. CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions) and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

OS is defined as the time from the date of first study drug administration to the date of death. Participants without documentation of death at the time of analysis were censored at the date when they were last known to be alive.

For each participant, the best percentage of tumor reduction from baseline in the sum of the diameter was calculated.

The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors. The score is obtained by the formula: 3 \* percentage of strongly staining nuclei + 2 \* percentage of moderately staining nuclei + percentage of weakly staining nuclei, giving a range of 0 to 300. The 600 H-score is based on the sum of the 0 to 300 H-score for cytoplasmic staining and the 0 to 300 H-score for apical staining

Blood samples were to be collected predose to evaluate ATA.

Millennium Pharmaceuticals, Inc.

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Participants who either received MLN0264 1.2 mg/kg as starting dose, or 1.5 mg/kg, or 1.8 mg/kg infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle of Phase 1, for up to 1 year or until disease progression or unacceptable toxicity.

Phase 1: All Participants

Between 45 to 78 years

Age, Customized

Race (NIH/OMB)

Japan

Taiwan

Korea, Republic of

Colon cancer

Rectal cancer

Gastric cancer

Lymphovascular invasion

Invasive ductal carcinoma of the pancreas

Moderately differentiated ductal adenocarcinoma

Adenocarcinoma not otherwise specified

Tubular adenocarcinoma

Moderately differentiated and descending colon

Histological classification included moderately differentiated adenocarcinoma (colon and rectal cancer); intestinal type adenocarcinoma (gastric cancer); adenocarcinoma with lymphovascular invasion; invasive ductal carcinoma of the pancreas, moderately differentiated ductal adenocarcinoma, adenocarcinoma not otherwise specified, tubular adenocarcinoma, and moderately differentiated adenocarcinoma of the transverse and descending colon.

Histological classification

Participants With Prior Medical Condition

With Surgical History

Without Surgical History

Participants With Surgical History

Participants With Prior Anticancer Therapy

With prior radiation therapy

Without prior radiation therapy

Participants With Prior Radiation Therapy

ECOG performance status is used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (\<) 50 percent (%) of the time; 3= in bed for greater than (\>) 50% of the time; 4= 100% bedridden; 5= dead.

Eastern Cooperative Oncology Group (ECOG) Therapy

Safety population included all participants who received any amount of study drug.

Medical Director

Safety population includes all participants who received any amount of study drug.

Phase 1- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE)

Phase 1- Number of Participants Reporting One or More Serious Adverse Events (SAE)

The DLT-Evaluable population included all participants who either experienced DLT during Cycle 1 or received their scheduled Cycle 1 dose and completed all study procedures in Cycle 1 without DLT.

Phase 1- Number of Participants Experiencing Dose-limiting Toxicities (DLTs)

Serum Chemistry

Hematology

Urinalysis

Coagulation

Phase 1- Number of Participants With Markedly Abnormal Laboratory Values

Phase 1- Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Phase 1- Recommended Phase 2 Dose (RP2D)

MLN0264 1.2 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity

Phase 1: MLN0264 1.2 mg/kg

MLN0264 1.5 mg/kg, infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity

Phase 1: MLN0264 1.5 mg/kg

MLN0264 1.8 mg/kg, infusion, intravenously, over 30 minutes on Day 1 of every 3 week cycle during the Phase 1, for up to 1 year or until disease progression or unacceptable toxicity

Phase 1: MLN0264 1.8 mg/kg

The Pharmacokinetic (PK) evaluable population included all participants who received greater than or equal to (\>=1) dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure.

Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for MLN0264

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available.

Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MLN0264

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure.

Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264

Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 1 Day 1 PK assessment were available.

Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264

Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264

Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm as none of the participants had data evaluable for this measure.

Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264

Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264

Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters.

Phase 1: Cycle 1- Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb)

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day 1 PK assessment were available.

Phase 1: Cycle 2- Cmax: Maximum Observed Serum Concentration for TAb

Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb

Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.

Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.

Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb

Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb

Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.

Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb

Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters.

Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE)

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day 1 PK assessment were available.

Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MMAE

Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE

Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.

Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE

The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Olaparib and Ramucirumab in Treating Patients With Metastatic or Locally Recurrent Gastric or Gastroesophageal Junction Cancer That Cannot Be Removed by Surgery	NCT03008278	Metastatic Esop... Metastatic Gast... Metastatic Gast... Recurrent Esoph... Recurrent Gastr... Recurrent Gastr... Stage III Esoph... Stage III Gastr... Stage IV Esopha... Stage IV Gastri... Unresectable Es... Unresectable Ga... Unresectable Ga...	Olaparib Ramucirumab	18 Years -	National Cancer Institute (NCI)
Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer	NCT01142388	Metastatic Esop... Metastatic Esop... Metastatic Gast... Recurrent Esoph... Recurrent Esoph... Recurrent Esoph... Recurrent Gastr... Stage IV Esopha...	Cixutumumab Laboratory Biom... Paclitaxel Pharmacological...	18 Years -	National Cancer Institute (NCI)
MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C	NCT02391038	Advanced Gastro... Gastroesophagea... Recurrent Gastr... Recurrent Gastr... Metastatic Gast... Metastatic Gast... Recurrent Gastr...	MLN0264	18 Years -	Takeda
IRX-2, Cyclophosphamide, and Pembrolizumab in Treating Participants With Recurrent or Metastatic Gastric or Gastroesophageal Junction Cancer	NCT03918499	Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Metastatic Gast... Metastatic Gast... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Recurrent Gastr... Recurrent Gastr...	Cyclophosphamid... Cytokine-based ... Pembrolizumab	18 Years -	City of Hope Medical Center
MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C	NCT02391038	Advanced Gastro... Gastroesophagea... Recurrent Gastr... Recurrent Gastr... Metastatic Gast... Metastatic Gast... Recurrent Gastr...	MLN0264	18 Years -	Takeda

Spots Global Cancer Trial Database for recurrent gastroesophageal junction adenocarcinoma