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

NCT02391038 | Terminated Phase 1 Results

• 3 other identifiers: C26004U1111-1164-1438JapicCTI-152851
• Study Type: interventional
• Target: 12
• Locations: 3 countries
• Sites: 4

Brief Summary

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).

Conditions

Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

Keywords

MLN0264; Advanced gastrointestinal carcinoma

Outcome Measures

Primary Outcomes (37)

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

  Phase 1: Baseline through 30 days after the last dose of study drug (approximately up to 35 weeks)

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

  Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

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

  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.

  Phase 1: Up to Cycle 1 (3 weeks)

• Phase 1- Number of Participants With Markedly Abnormal Laboratory Values

  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.

  Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

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

  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 \[bpm\]).

  Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

• Phase 1- Recommended Phase 2 Dose (RP2D)

  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.

  Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

• 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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

• 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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

• 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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

• 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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

• 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 MMAE

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

• 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 MMAE

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose

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

  Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose

• Phase 2- Overall Response Rate

  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.

  Baseline until end of study treatment (approximately 1 year)

Secondary Outcomes (14)

• Phase 1- Number of Participants With Antitherapeutic Antibodies (ATAs)

  Day 1 of Cycle 1, 2, 3, 4: predose

• Phase 1- Disease Response Based on the Investigator's Assessment

  Phase 1: Day 21 of every other cycle (Cycle 2, 4, 6, 8) up to End of treatment (EOT) (Cycle10 or week 30)

• Phase 2- Percentage of Participants Who Experience at Least One TEAE

  Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year)

• Phase 2- Percentage of Participants Who Experience at Least One SAE

  Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year)

• Phase 2- Number of Participants With Markedly Abnormal Laboratory Values

  Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year)

Study Arms (1)

MLN0264

EXPERIMENTAL

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.

Drug: MLN0264

Interventions

MLN0264 DRUG

MLN0264 IV.

MLN0264

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has Diagnosis of GI carcinoma with Immunohistochemistry/ Immunohistochemical (IHC) evidence of expression of GCC protein (H-score of 10 or greater), for which standard treatment is no longer effective or does not offer curative or life-prolonging potential.
• Has completed prior chemotherapy, immunotherapy or radiation therapy at least 4 weeks prior to enrollment (except for Avastin \[bevacizumab\] for which at least 8 weeks from its last administration should elapse prior to enrollment).
• Histologically confirmed metastatic or advanced inoperable adenocarcinoma of the stomach or gastroesophageal junction with IHC evidence of expression of GCC indicated by an H-score of 10 or greater.
• Has completed prior chemotherapy, immunotherapy or radiation therapy at least 4 weeks prior to enrollment.
• Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.
• Has Eastern Cooperative Oncology Group performance status of 0 or 1 (within 14 days prior to enrollment).
• Females must be 1-year postmenopausal, or even if surgically sterile, agree to use other acceptable forms of birth control.
• Has adequate organ and hematological function.
• Has resolution of all toxic effects of prior treatments except alopecia to Grade 0 or 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03

You may not qualify if:

• Has Concurrent treatment or treatment within 4 weeks of study entry with any other investigational agent.
• Female participants who are in the lactation period, even if they discontinue breastfeeding, or have a positive pregnancy test during the Screening period.
• Has uncontrolled, clinically significant, symptomatic cardiovascular disease within 6 months prior to enrollment.
• Has treatment with any medication that has a clinically relevant potential risk of prolonging the QT interval or inducing Torsades de Pointes that cannot be discontinued or switched to a different medication prior to starting study drug.
• Participants with electrocardiogram (ECG) abnormalities considered by the investigator to be clinically -significant, or repeated baseline prolongation of the rate-corrected QT interval millisecond (msec) of electrocardiograph (QTc).
• Ongoing or clinically significant active infection.
• Has signs of peripheral neuropathy.
• Concomitant chemotherapy, hormonal therapy, immunotherapy, or any other form of cancer treatment.
• Use of strong cytochrome P450 (CYP) 3A4 inhibitors within 2 weeks before the first dose of study drug.
• Has any preexisting medical condition of sufficient severity to prevent full compliance with the study.
• Has past or concurrent history of neoplasm other than GI carcinoma (phase 1) or gastric adenocarcinoma (phase 2), except for curatively treated nonmelanoma skin cancer or in situ carcinoma of the cervix uteri.
• Known diagnosis of human immunodeficiency virus (HIV) infection.
• Has asymptomatic brain metastases.
• Has an alcohol or substance abuse disorder.
• Has positive test for hepatitis B surface antigen.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (4)

Unknown Facility

Kashiwa-shi, Chiba, Japan

Location

Unknown Facility

Minatoku, Tokyo-To, Japan

Location

Unknown Facility

Seoul, Gyeonggi-do, South Korea

Location

Unknown Facility

Taipei, Taipei, Taiwan

Location

MeSH Terms

Interventions

indusatumab

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical science

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2014
• First Posted: March 18, 2015
• Study Start: December 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: March 29, 2017
• Results First Posted: March 29, 2017

Record last verified: 2017-02

Locations

TW (1); JP (2); KR (1)