A Study of MLN0264 in Patients With Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

The purpose of this study is to assess the efficacy, safety and tolerability of MLN0264 in patients with advanced or metastatic guanylyl cyclase C (GCC)-positive adenocarcinoma of the pancreas.

Detailed description public domain (ClinicalTrials.gov)

The drug being tested in this study is called MLN0264. MLN0264 is being tested to treat tumors in people who have metastatic adenocarcinoma of the pancreas expressing guanylyl cyclase C (GCC). This study will assess tumor size reduction in patients who are administered MLN0264. The study will enroll 42 to 81 patients. All participants will be administered MLN0264 at 1.8 mg/kg as a single, 30-minute, intravenous (IV) infusion on Day 1 of each 3-week treatment cycle, followed by a rest period of 20 days. Participants will continue to receive MLN0264 for up to 1 year or until disease progression or unacceptable toxicity occurs. This multi-centre trial will be conducted worldwide. The overall time to participate in this study is approximately 19 months. Participants will make 3 to 6 visits to the clinic per treatment cycle, an end-of-treatment visit will occur 30 days after the last dose of study medication, and follow-up assessments will occur every 12 weeks until death or 6 months after the last patient completes treatment - whichever occurs first.

Intervention public domain (ClinicalTrials.gov)

Drug: MLN0264. MLN0264 IV infusion

Arm public domain (ClinicalTrials.gov)

MLN0264 1.8 mg/kg (experimental): MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.

Primary outcome public domain (ClinicalTrials.gov)

Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST). ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. Time frame: Day 21, every other cycle, starting with Cycle 2 until disease progression, death or study closure (Up to 16 months).

Secondary outcome public domain (ClinicalTrials.gov)

Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings. Time frame: Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 7.9 months).

Secondary outcome public domain (ClinicalTrials.gov)

Number of Participants With Potentially Clinically Significant Vital Signs Findings. Time frame: Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 7.9 months).

Secondary outcome public domain (ClinicalTrials.gov)

Progression Free Survival (PFS). Time frame: Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Up to 13.9 months).

Secondary outcome public domain (ClinicalTrials.gov)

Duration of Response. Time frame: From first documented response until disease progression (Up to 16 months).

Secondary outcome public domain (ClinicalTrials.gov)

Disease Control Rate. Time frame: Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Up to 13.9 months).

Secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS). Time frame: Until death or 6 months after the last patient completes treatment-whichever occurs first (Up to 16 months).

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: 1. Male or female participants 18 years of age or older when written informed consent is obtained. 2. Histologically confirmed metastatic or advanced inoperable adenocarcinoma of the pancreas with immunohistochemistry (IHC) evidence of guanylyl cyclase C (GCC) expression indicated by an H-score of 10 or greater. 3. Treatment with 1 or more prior chemotherapies for advanced or metastatic adenocarcinoma of the pancreas. 4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. All scans and x-rays used to document measurable disease must be done within 28 days before enrollment (ascites and bone lesions are not considered measureable disease). 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days before enrollment. 6. Female participants who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.) Male participants, even if surgically sterilized (ie, status postvasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception.) 7. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care. 8. Adequate organ and hematological function as evidenced by the following laboratory values within 14 days before enrollment: * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Hemoglobin ≥ 9 g/dL * Activated partial thromboplastin time (aPTT) ≤ …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 43 participants (actual).

Why stopped public domain (ClinicalTrials.gov)

Business Decision, No Safety or Efficacy Concerns

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) [Day 21, every other cycle, starting with Cycle 2 until disease progression, death or study closure (Up to 16 months)]. Number, percentage of participants. MLN0264 1.8 mg/kg (GCC Low) (n=11): 0; MLN0264 1.8 mg/kg (GCC Intermediate) (n=13): 8; MLN0264 1.8 mg/kg (GCC High) (n=15): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings [Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 7.9 months)]. Number, Participants. Chemistry: MLN0264 1.8 mg/kg (n=43): 20. Hematology: MLN0264 1.8 mg/kg (n=43): 16. Coagulation: MLN0264 1.8 mg/kg (n=43): 23. Urinalysis: MLN0264 1.8 mg/kg (n=43): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Participants With Potentially Clinically Significant Vital Signs Findings [Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 7.9 months)]. Number, Participants. MLN0264 1.8 mg/kg (n=43): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression Free Survival (PFS) [Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Up to 13.9 months)]. Median, days (Full Range). MLN0264 1.8 mg/kg (GCC Low) (n=11): 39 (9 to 82); MLN0264 1.8 mg/kg (GCC Intermediate) (n=13): 42 (21 to 218); MLN0264 1.8 mg/kg (GCC High) (n=15): 41 (16 to 137).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Duration of Response [From first documented response until disease progression (Up to 16 months)]. Median, days (Full Range). MLN0264 1.8 mg/kg (n=1): 103 (103 to 103).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease Control Rate [Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Up to 13.9 months)]. Number, percentage of participants. MLN0264 1.8 mg/kg (GCC Low) (n=11): 0; MLN0264 1.8 mg/kg (GCC Intermediate) (n=13): 23; MLN0264 1.8 mg/kg (GCC High) (n=15): 20.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) [Until death or 6 months after the last patient completes treatment-whichever occurs first (Up to 16 months)]. Median, days (Full Range). MLN0264 1.8 mg/kg (GCC Low) (n=11): 162 (36 to 282); MLN0264 1.8 mg/kg (GCC Intermediate) (n=15): 140 (43 to 443); MLN0264 1.8 mg/kg (GCC High) (n=17): 162 (49 to 435).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Cmax: Maximum Observed Serum Concentration for MLN0264 [Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Serum Concentration of Monomethyl Auristatin E (MMAE) [Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.]. Mean, ng/mL (Standard Deviation). Cycle 1 Day 1, Pre-Dose: MLN0264 1.8 mg/kg (n=43): 0.000 (0.0000). Cycle 1 Day 1, 10 Minutes Post-Dose: MLN0264 1.8 mg/kg (n=43): 0.296 (0.1624). Cycle 1 Day 1, 4 Hours Post-Dose: MLN0264 1.8 mg/kg (n=43): 2.438 (1.3015). Cycle 1 Day 3, 48 Hours Post-Dose (n=41): MLN0264 1.8 mg/kg (n=43): 5.205 (2.8110). Cycle 1 Day 4, 72 Hours Post-Dose (n=39): MLN0264 1.8 mg/kg (n=43): 4.918 (2.3653). Cycle 1 Day 8, 168 Hours Post-Dose (n=43): MLN0264 1.8 mg/kg (n=43): 2.994 (2.1173). Cycle 1 Day 15, 336 Hours Post-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 0.580 (0.5073). Cycle 2 Day 1, Pre-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 0.128 (0.1304). Cycle 2 Day 1, 10 Minutes Post-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 0.405 (0.3351). Cycle 2 Day 1, 4 Hours Post-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 2.665 (1.6053). Cycle 2 Day 3, 48 Hours Post-Dose (n=34): MLN0264 1.8 mg/kg (n=43): 6.223 (3.5926). Cycle 2 Day 4, 72 Hours Post-Dose (n=32): MLN0264 1.8 mg/kg (n=43): 5.808 (3.6296). Cycle 2 Day 8, 168 Hours Post-Dose (n=34): MLN0264 1.8 mg/kg (n=43): 2.789 (2.0437). Cycle 2 Day 15, 336 Hours Post-Dose (n=28): MLN0264 1.8 mg/kg (n=43): 0.560 (0.5332). Cycle 3 Day 1, Pre-Dose (n=9): MLN0264 1.8 mg/kg (n=43): 0.145 (0.1318). Cycle 3 Day 1, 10 Minutes Post-Dose (n=9): MLN0264 1.8 mg/kg (n=43): 0.395 (0.3514). Cycle 3 Day 1, 4 Hours Post-Dose (n=9): MLN0264 1.8 mg/kg (n=43): 2.237 (1.6402). Cycle 3 Day 3, 48 Hours Post-Dose (n=8): MLN0264 1.8 mg/kg (n=43): 6.563 (5.2034). Cycle 3 Day 4, 72 Hours Post-Dose (n=8): MLN0264 1.8 mg/kg (n=43): 6.563 (6.2902). Cycle 3 Day 8, 168 Hours Post-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 2.826 (2.0234). Cycle 3 Day 15, 336 Hours Post-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 1.155 (1.2808). Cycle 4 Day 1, Pre-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 0.232 (0.2877). Cycle 4 Day 1, 10 Minutes Post-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 0.446 (0.4029). Cycle 5 Day 1, Pre-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 0.090 (0.0594). Cycle 5 Day 1, 10 Minutes Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 0.249 (0.1004). Cycle 6 Day 1, Pre-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 0.105 (0.0469). Cycle 6 Day 1, 10 Minutes Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 0.269 (0.1037). Cycle 6 Day 4, 72 Hours Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 4.234 (1.3134). Cycle 6 Day 8, 168 Hours Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 2.002 (0.9691). Cycle 7 Day 1, Pre-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 0.125 (0.0365). Cycle 7 Day 1, 10 Minutes Post-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 0.277 (0.0806). Cycle 8 Day 1, Pre-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 0.108 (0.0288). Cycle 8 Day 1, 10 Minute Post-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 0.257 (0.0481). Cycle 9 Day 1, Pre-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 0.050 (0.0179). Cycle 9 Day 1, 10

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC) [From pre-screening through end of study (approximately 18 months)]. Mean, scores on a scale (Full Range). MLN0264 1.8 mg/kg (GCC Low) (n=11): 29.6 (10 to 55); MLN0264 1.8 mg/kg (GCC Intermediate) (n=15): 84.0 (60 to 110); MLN0264 1.8 mg/kg (GCC High) (n=17): 204.2 (120 to 355).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From the first dose through 30 days after the last dose of study medication (Up to 7.9 months)]. Number, Participants. AEs: MLN0264 1.8 mg/kg (GCC Low) (n=11): 11; MLN0264 1.8 mg/kg (GCC Intermediate) (n=15): 15; MLN0264 1.8 mg/kg (GCC High) (n=17): 17. SAEs: MLN0264 1.8 mg/kg (GCC Low) (n=11): 3; MLN0264 1.8 mg/kg (GCC Intermediate) (n=15): 7; MLN0264 1.8 mg/kg (GCC High) (n=17): 9.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

MLN0264 Serum Concentrations [Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.]. Mean, μg/mL (Standard Deviation). Cycle 1 Day 1, Pre-Dose: MLN0264 1.8 mg/kg (n=43): 0.000 (0.0000). Cycle 1 Day 1, 10 Minutes Post-Dose: MLN0264 1.8 mg/kg (n=43): 36.647 (10.0936). Cycle 1 Day 1, 4 Hours Post-Dose: MLN0264 1.8 mg/kg (n=43): 27.898 (8.4886). Cycle 1 Day 3, 48 Hours Post-Dose (n=41): MLN0264 1.8 mg/kg (n=43): 6.950 (1.9173). Cycle 1 Day 4, 72 Hours Post-Dose (n=39): MLN0264 1.8 mg/kg (n=43): 4.758 (1.5349). Cycle 1 Day 8, 168 Hours Post-Dose (n=43): MLN0264 1.8 mg/kg (n=43): 1.563 (0.5818). Cycle 1 Day 15, 336 Hours Post-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 0.582 (0.2331). Cycle 2 Day 1, Pre-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 0.261 (0.1643). Cycle 2 Day 1, 10 Minutes Post-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 30.856 (9.9483). Cycle 2 Day 1, 4 Hours Post-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 26.691 (7.9664). Cycle 2 Day 3, 48 Hours Post-Dose (n=35): MLN0264 1.8 mg/kg (n=43): 7.021 (2.4977). Cycle 2 Day 4, 72 Hours Post-Dose (n=32): MLN0264 1.8 mg/kg (n=43): 4.432 (1.6115). Cycle 2 Day 8, 168 Hours Post-Dose (n=34): MLN0264 1.8 mg/kg (n=43): 1.681 (0.7800). Cycle 2 Day 15, 336 Hours Post-Dose (n=27): MLN0264 1.8 mg/kg (n=43): 0.692 (0.3038). Cycle 3 Day 1, Pre-Dose (n=9): MLN0264 1.8 mg/kg (n=43): 0.431 (0.1481). Cycle 3 Day 1, 10 Minutes Post-Dose (n=9): MLN0264 1.8 mg/kg (n=43): 34.978 (5.3350). Cycle 3 Day 1, 4 Hours Post-Dose (n=9): MLN0264 1.8 mg/kg (n=43): 26.393 (3.3557). Cycle 3 Day 3, 48 Hours Post-Dose (n=8): MLN0264 1.8 mg/kg (n=43): 9.486 (2.9593). Cycle 3 Day 4, 72 Hours Post-Dose (n=8): MLN0264 1.8 mg/kg (n=43): 6.579 (1.8102). Cycle 3 Day 8, 168 Hours Post-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 1.701 (0.4201). Cycle 3 Day 15, 336 Hours Post-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 0.890 (0.2276). Cycle 4 Day 1, Pre-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 0.490 (0.1881). Cycle 4 Day 1, 10 Minutes Post-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 37.166 (9.3823). Cycle 5 Day 1, Pre-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 0.446 (0.2197). Cycle 5 Day 1, 10 Minutes Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 31.060 (8.3802). Cycle 6 Day 1, Pre-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 0.412 (0.2183). Cycle 6 Day 1, 10 Minutes Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 23.204 (12.9564). Cycle 6 Day 4, 72 Hours Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 4.689 (0.9286). Cycle 6 Day 8, 168 Hours Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 1.410 (0.2504). Cycle 7 Day 1, Pre-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 0.277 (0.0863). Cycle 7 Day 1, 10 Minutes Post-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 34.560 (6.5337). Cycle 8 Day 1, Pre-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 2.047 (2.6517). Cycle 8 Day 1, 10 Minute Post-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 27.120 (4.8649). Cycle 9 Day 1, Pre-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 0.178 (0.0467). Cycle 9 Day 1, 10 Minutes Pos

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Serum Concentration of Total Antibodies (Conjugated and Unconjugated) [Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.]. Mean, μg/mL (Standard Deviation). Cycle 1 Day 1, Pre-Dose: MLN0264 1.8 mg/kg (n=43): 0.000 (0.0000). Cycle 1 Day 1, 10 Minutes Post-Dose: MLN0264 1.8 mg/kg (n=43): 37.599 (9.4299). Cycle 1 Day 1, 4 Hours Post-Dose: MLN0264 1.8 mg/kg (n=43): 32.974 (8.1824). Cycle 1 Day 3, 48 Hours Post-Dose (n=41): MLN0264 1.8 mg/kg (n=43): 14.051 (4.0368). Cycle 1 Day 4, 72 Hours Post-Dose (n=39): MLN0264 1.8 mg/kg (n=43): 10.546 (3.6488). Cycle 1 Day 8, 168 Hours Post-Dose (n=43): MLN0264 1.8 mg/kg (n=43): 5.252 (1.7703). Cycle 1 Day 15, 336 Hours Post-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 2.958 (1.1577). Cycle 2 Day 1, Pre-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 1.668 (0.7608). Cycle 2 Day 1, 10 Minutes Post-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 35.963 (10.9226). Cycle 2 Day 1, 4 Hours Post-Dose (n=37): MLN0264 1.8 mg/kg (n=43): 32.134 (9.7822). Cycle 2 Day 3, 48 Hours Post-Dose (n=35): MLN0264 1.8 mg/kg (n=43): 14.194 (4.8398). Cycle 2 Day 4, 72 Hours Post-Dose (n=32): MLN0264 1.8 mg/kg (n=43): 10.948 (4.2741). Cycle 2 Day 8, 168 Hours Post-Dose (n=34): MLN0264 1.8 mg/kg (n=43): 6.312 (2.7008). Cycle 2 Day 15, 336 Hours Post-Dose (n=27): MLN0264 1.8 mg/kg (n=43): 3.923 (1.7465). Cycle 3 Day 1, Pre-Dose (n=9): MLN0264 1.8 mg/kg (n=43): 2.654 (1.0757). Cycle 3 Day 1, 10 Minutes Post-Dose (n=9): MLN0264 1.8 mg/kg (n=43): 39.500 (6.0580). Cycle 3 Day 1, 4 Hours Post-Dose (n=9): MLN0264 1.8 mg/kg (n=43): 37.549 (8.2628). Cycle 3 Day 3, 48 Hours Post-Dose (n=8): MLN0264 1.8 mg/kg (n=43): 19.181 (3.7260). Cycle 3 Day 4, 72 Hours Post-Dose (n=8): MLN0264 1.8 mg/kg (n=43): 15.808 (2.0102). Cycle 3 Day 8, 168 Hours Post-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 6.631 (3.8091). Cycle 3 Day 15, 336 Hours Post-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 5.279 (1.9171). Cycle 4 Day 1, Pre-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 3.252 (1.3859). Cycle 4 Day 1, 10 Minutes Post-Dose (n=7): MLN0264 1.8 mg/kg (n=43): 42.194 (8.8085). Cycle 5 Day 1, Pre-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 2.734 (1.2045). Cycle 5 Day 1, 10 Minutes Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 44.244 (27.1286). Cycle 6 Day 1, Pre-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 2.854 (1.7255). Cycle 6 Day 1, 10 Minutes Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 36.304 (12.1646). Cycle 6 Day 4, 72 Hours Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 12.667 (3.4384). Cycle 6 Day 8, 168 Hours Post-Dose (n=5): MLN0264 1.8 mg/kg (n=43): 8.040 (3.1264). Cycle 7 Day 1, Pre-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 1.997 (0.7877). Cycle 7 Day 1, 10 Minutes Post-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 37.130 (4.9922). Cycle 8 Day 1, Pre-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 1.901 (0.5834). Cycle 8 Day 1, 10 Minute Post-Dose (n=2): MLN0264 1.8 mg/kg (n=43): 66.240 (43.7558). Cycle 9 Day 1, Pre-Dose (n=2): MLN0264 1.8 mg/kg (n=

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Percentage of Participants With Reduction From Baseline in Tumor Size [Day 21 of each 21-day cycle, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Approximately 13.9 months)]. Number, percentage of participants. MLN0264 1.8 mg/kg (GCC Low) (n=10): 50; MLN0264 1.8 mg/kg (GCC Intermediate) (n=15): 64; MLN0264 1.8 mg/kg (GCC High) (n=15): 73.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Participants With Antitherapeutic Antibodies (ATA) [Pre-dose of each 21 day cycle and 30 days after last dose of study medication (Up to 7.9 months)]. Number, Participants. MLN0264 1.8 mg/kg (GCC Low) (n=11): 0; MLN0264 1.8 mg/kg (GCC Intermediate) (n=15): 0; MLN0264 1.8 mg/kg (GCC High) (n=17): 0.