Trial Outcomes & Findings for A Study MLN2480 in Combination With MLN0128 or Alisertib, or Paclitaxel, or Cetuximab, or Irinotecan in Adult Participants With Advanced Nonhematologic Malignancies (NCT NCT02327169)

Last Updated: 2020-02-25

Results Overview

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An SAE means any untoward medical occurrence that at any dose results in death, is life-threatening, requires in patient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

81 participants

Primary outcome timeframe

From Day 1, Cycle 1 through 30 days after the last dose of study drug (up to 13 months)

Results posted on

2020-02-25

Participant Flow

Participants took part in the study at 14 investigative sites in the United States, France, Spain, and United Kingdom from 14 September 2016 to 02 July 2018.

Participants with a diagnosis of advanced nonhematologic malignancies were enrolled in one of the five arm groups: MLN2480 + MLN0128, MLN2480 + Alisertib, MLN2480 + Paclitaxel, MLN2480 + Cetuximab, MLN2480 + Irinotecan.

Participant milestones

Participant milestones
Measure	MLN2480 100 mg + MLN0128 2 mg Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and MLN0128 2 mg, capsules, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles.	MLN2480 100 mg + Alisertib 30 mg Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 160 mg + Alisertib 30 mg Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 200 mg + Alisertib 30 mg Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Alisertib 40 mg Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 40 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Paclitaxel 80 mg/m^2 Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 milligram per square meter (mg/m\^2), intravenous (IV) infusion, once weekly (QW) for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 160 mg + Paclitaxel 80 mg/m^2 Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 200 mg + Paclitaxel 80 mg/m^2 Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Paclitaxel 80 mg/m^2 Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 600 mg + Paclitaxel 80 mg/m^2 Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Cetuximab 250 mg/m^2 Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	MLN2480 600 mg + Cetuximab 250 mg/m^2 Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	ML2480 300 mg + Irinotecan 180 mg/m^2 Dose Escalation Phase: MLN2480 300 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	ML2480 400 mg + Irinotecan 180 mg/m^2 Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	Dose Expansion: MLN2480 600 mg + Paclitaxel 80 mg/m^2 Dose Expansion Phase: MLN2480 600 mg, tablets, orally, once per week on Days 2, 9, 16 and 23 of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, once on 1, 8, and 15 of a 28-day cycle for up to 12 cycles.
Overall Study STARTED	4	3	7	3	8	4	3	4	6	8	6	7	1	7	10
Overall Study COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	4	3	7	3	8	4	3	4	6	8	6	7	1	7	10

Reasons for withdrawal

Reasons for withdrawal
Measure	MLN2480 100 mg + MLN0128 2 mg Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and MLN0128 2 mg, capsules, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles.	MLN2480 100 mg + Alisertib 30 mg Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 160 mg + Alisertib 30 mg Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 200 mg + Alisertib 30 mg Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Alisertib 40 mg Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 40 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Paclitaxel 80 mg/m^2 Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 milligram per square meter (mg/m\^2), intravenous (IV) infusion, once weekly (QW) for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 160 mg + Paclitaxel 80 mg/m^2 Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 200 mg + Paclitaxel 80 mg/m^2 Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Paclitaxel 80 mg/m^2 Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 600 mg + Paclitaxel 80 mg/m^2 Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Cetuximab 250 mg/m^2 Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	MLN2480 600 mg + Cetuximab 250 mg/m^2 Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	ML2480 300 mg + Irinotecan 180 mg/m^2 Dose Escalation Phase: MLN2480 300 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	ML2480 400 mg + Irinotecan 180 mg/m^2 Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	Dose Expansion: MLN2480 600 mg + Paclitaxel 80 mg/m^2 Dose Expansion Phase: MLN2480 600 mg, tablets, orally, once per week on Days 2, 9, 16 and 23 of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, once on 1, 8, and 15 of a 28-day cycle for up to 12 cycles.
Overall Study Progressive Disease	1	3	4	3	4	3	3	3	4	4	4	3	1	3	3
Overall Study Adverse Event	2	0	1	0	1	0	0	0	0	2	0	3	0	2	1
Overall Study Symptomatic Deterioration	0	0	1	0	1	1	0	0	2	1	0	0	0	2	1
Overall Study Reason Not Specified	0	0	1	0	0	0	0	0	0	1	2	1	0	0	2
Overall Study Withdrawal by Subject	1	0	0	0	1	0	0	1	0	0	0	0	0	0	3
Overall Study Lost to Follow-up	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Number analyzed is the number of participants with data available for height.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MLN2480 100 mg + MLN0128 2 mg n=4 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and MLN0128 2 mg, capsules, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles.	MLN2480 100 mg + Alisertib 30 mg n=3 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 160 mg + Alisertib 30 mg n=7 Participants Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 200 mg + Alisertib 30 mg n=3 Participants Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Alisertib 40 mg n=8 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 40 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Paclitaxel 80 mg/m^2 n=4 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 milligram per square meter (mg/m\^2), intravenous (IV) infusion, once weekly (QW) for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 160 mg + Paclitaxel 80 mg/m^2 n=3 Participants Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 200 mg + Paclitaxel 80 mg/m^2 n=4 Participants Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Paclitaxel 80 mg/m^2 n=6 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 600 mg + Paclitaxel 80 mg/m^2 n=8 Participants Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Cetuximab 250 mg/m^2 n=6 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	MLN2480 600 mg + Cetuximab 250 mg/m^2 n=7 Participants Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	ML2480 300 mg + Irinotecan 180 mg/m^2 n=1 Participants Dose Escalation Phase: MLN2480 300 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	ML2480 400 mg + Irinotecan 180 mg/m^2 n=7 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	Dose Expansion: MLN2480 600 mg + Paclitaxel 80 mg/m^2 n=10 Participants Dose Expansion Phase: MLN2480 600 mg, tablets, orally, once per week on Days 2, 9, 16 and 23 of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, once on 1, 8, and 15 of a 28-day cycle for up to 12 cycles.	Total n=81 Participants Total of all reporting groups
Age, Continuous	57.5 years n=4 Participants	48.0 years n=3 Participants	60.9 years n=7 Participants	51.0 years n=3 Participants	68.0 years n=8 Participants	66.0 years n=4 Participants	60.3 years n=3 Participants	70.0 years n=4 Participants	54.2 years n=6 Participants	65.9 years n=8 Participants	52.8 years n=6 Participants	60.1 years n=7 Participants	62.0 years n=1 Participants	62.3 years n=7 Participants	63.9 years n=10 Participants	62.3 years n=81 Participants
Sex: Female, Male Female	3 Participants n=4 Participants	3 Participants n=3 Participants	4 Participants n=7 Participants	1 Participants n=3 Participants	6 Participants n=8 Participants	2 Participants n=4 Participants	2 Participants n=3 Participants	3 Participants n=4 Participants	5 Participants n=6 Participants	4 Participants n=8 Participants	2 Participants n=6 Participants	4 Participants n=7 Participants	0 Participants n=1 Participants	3 Participants n=7 Participants	5 Participants n=10 Participants	47 Participants n=81 Participants
Sex: Female, Male Male	1 Participants n=4 Participants	0 Participants n=3 Participants	3 Participants n=7 Participants	2 Participants n=3 Participants	2 Participants n=8 Participants	2 Participants n=4 Participants	1 Participants n=3 Participants	1 Participants n=4 Participants	1 Participants n=6 Participants	4 Participants n=8 Participants	4 Participants n=6 Participants	3 Participants n=7 Participants	1 Participants n=1 Participants	4 Participants n=7 Participants	5 Participants n=10 Participants	34 Participants n=81 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=7 Participants	1 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=4 Participants	1 Participants n=3 Participants	0 Participants n=4 Participants	0 Participants n=6 Participants	0 Participants n=8 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	0 Participants n=1 Participants	0 Participants n=7 Participants	0 Participants n=10 Participants	2 Participants n=81 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=4 Participants	3 Participants n=3 Participants	7 Participants n=7 Participants	0 Participants n=3 Participants	8 Participants n=8 Participants	3 Participants n=4 Participants	1 Participants n=3 Participants	4 Participants n=4 Participants	5 Participants n=6 Participants	7 Participants n=8 Participants	5 Participants n=6 Participants	4 Participants n=7 Participants	1 Participants n=1 Participants	7 Participants n=7 Participants	6 Participants n=10 Participants	65 Participants n=81 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=7 Participants	2 Participants n=3 Participants	0 Participants n=8 Participants	1 Participants n=4 Participants	1 Participants n=3 Participants	0 Participants n=4 Participants	1 Participants n=6 Participants	1 Participants n=8 Participants	1 Participants n=6 Participants	3 Participants n=7 Participants	0 Participants n=1 Participants	0 Participants n=7 Participants	4 Participants n=10 Participants	14 Participants n=81 Participants
Race/Ethnicity, Customized White	4 Participants n=4 Participants	3 Participants n=3 Participants	6 Participants n=7 Participants	1 Participants n=3 Participants	8 Participants n=8 Participants	4 Participants n=4 Participants	2 Participants n=3 Participants	4 Participants n=4 Participants	3 Participants n=6 Participants	6 Participants n=8 Participants	6 Participants n=6 Participants	4 Participants n=7 Participants	1 Participants n=1 Participants	7 Participants n=7 Participants	5 Participants n=10 Participants	64 Participants n=81 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=4 Participants	1 Participants n=3 Participants	0 Participants n=4 Participants	1 Participants n=6 Participants	0 Participants n=8 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	0 Participants n=1 Participants	0 Participants n=7 Participants	0 Participants n=10 Participants	2 Participants n=81 Participants
Race/Ethnicity, Customized Other	0 Participants n=4 Participants	0 Participants n=3 Participants	1 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=4 Participants	1 Participants n=6 Participants	0 Participants n=8 Participants	0 Participants n=6 Participants	0 Participants n=7 Participants	0 Participants n=1 Participants	0 Participants n=7 Participants	1 Participants n=10 Participants	3 Participants n=81 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=7 Participants	2 Participants n=3 Participants	0 Participants n=8 Participants	0 Participants n=4 Participants	0 Participants n=3 Participants	0 Participants n=4 Participants	1 Participants n=6 Participants	2 Participants n=8 Participants	0 Participants n=6 Participants	3 Participants n=7 Participants	0 Participants n=1 Participants	0 Participants n=7 Participants	4 Participants n=10 Participants	12 Participants n=81 Participants
Height	168.9 centimetres (cm) n=4 Participants • Number analyzed is the number of participants with data available for height.	163.4 centimetres (cm) n=3 Participants • Number analyzed is the number of participants with data available for height.	166.7 centimetres (cm) n=6 Participants • Number analyzed is the number of participants with data available for height.	160.3 centimetres (cm) n=2 Participants • Number analyzed is the number of participants with data available for height.	164.5 centimetres (cm) n=8 Participants • Number analyzed is the number of participants with data available for height.	167.0 centimetres (cm) n=4 Participants • Number analyzed is the number of participants with data available for height.	167.7 centimetres (cm) n=3 Participants • Number analyzed is the number of participants with data available for height.	166.3 centimetres (cm) n=4 Participants • Number analyzed is the number of participants with data available for height.	159.7 centimetres (cm) n=6 Participants • Number analyzed is the number of participants with data available for height.	167.3 centimetres (cm) n=8 Participants • Number analyzed is the number of participants with data available for height.	169.8 centimetres (cm) n=6 Participants • Number analyzed is the number of participants with data available for height.	167.4 centimetres (cm) n=7 Participants • Number analyzed is the number of participants with data available for height.	182.5 centimetres (cm) n=1 Participants • Number analyzed is the number of participants with data available for height.	172.3 centimetres (cm) n=5 Participants • Number analyzed is the number of participants with data available for height.	162.7 centimetres (cm) n=10 Participants • Number analyzed is the number of participants with data available for height.	164.7 centimetres (cm) n=77 Participants • Number analyzed is the number of participants with data available for height.
Weight	71.55 kilograms (kg) n=4 Participants • Number analyzed is the number of participants with data available for weight.	80.53 kilograms (kg) n=3 Participants • Number analyzed is the number of participants with data available for weight.	84.62 kilograms (kg) n=6 Participants • Number analyzed is the number of participants with data available for weight.	74.15 kilograms (kg) n=2 Participants • Number analyzed is the number of participants with data available for weight.	63.59 kilograms (kg) n=8 Participants • Number analyzed is the number of participants with data available for weight.	86.63 kilograms (kg) n=4 Participants • Number analyzed is the number of participants with data available for weight.	77.40 kilograms (kg) n=3 Participants • Number analyzed is the number of participants with data available for weight.	65.45 kilograms (kg) n=4 Participants • Number analyzed is the number of participants with data available for weight.	67.92 kilograms (kg) n=6 Participants • Number analyzed is the number of participants with data available for weight.	65.79 kilograms (kg) n=8 Participants • Number analyzed is the number of participants with data available for weight.	76.22 kilograms (kg) n=6 Participants • Number analyzed is the number of participants with data available for weight.	71.39 kilograms (kg) n=7 Participants • Number analyzed is the number of participants with data available for weight.	86.50 kilograms (kg) n=1 Participants • Number analyzed is the number of participants with data available for weight.	74.97 kilograms (kg) n=7 Participants • Number analyzed is the number of participants with data available for weight.	67.65 kilograms (kg) n=10 Participants • Number analyzed is the number of participants with data available for weight.	70.31 kilograms (kg) n=79 Participants • Number analyzed is the number of participants with data available for weight.
Body Surface Area (BSA)	1.818 square meters (m^2) n=4 Participants • Number analyzed is the number of participants with data available for body surface area.	1.906 square meters (m^2) n=3 Participants • Number analyzed is the number of participants with data available for body surface area.	1.961 square meters (m^2) n=6 Participants • Number analyzed is the number of participants with data available for body surface area.	1.817 square meters (m^2) n=2 Participants • Number analyzed is the number of participants with data available for body surface area.	1.698 square meters (m^2) n=8 Participants • Number analyzed is the number of participants with data available for body surface area.	2.003 square meters (m^2) n=4 Participants • Number analyzed is the number of participants with data available for body surface area.	1.884 square meters (m^2) n=3 Participants • Number analyzed is the number of participants with data available for body surface area.	1.732 square meters (m^2) n=4 Participants • Number analyzed is the number of participants with data available for body surface area.	1.726 square meters (m^2) n=6 Participants • Number analyzed is the number of participants with data available for body surface area.	1.738 square meters (m^2) n=8 Participants • Number analyzed is the number of participants with data available for body surface area.	1.893 square meters (m^2) n=6 Participants • Number analyzed is the number of participants with data available for body surface area.	1.814 square meters (m^2) n=7 Participants • Number analyzed is the number of participants with data available for body surface area.	2.094 square meters (m^2) n=1 Participants • Number analyzed is the number of participants with data available for body surface area.	1.925 square meters (m^2) n=5 Participants • Number analyzed is the number of participants with data available for body surface area.	1.740 square meters (m^2) n=10 Participants • Number analyzed is the number of participants with data available for body surface area.	1.846 square meters (m^2) n=77 Participants • Number analyzed is the number of participants with data available for body surface area.

PRIMARY outcome

Timeframe: From Day 1, Cycle 1 through 30 days after the last dose of study drug (up to 13 months)

Population: Safety population was defined as all participants who received any amount of MLN2480.

Outcome measures

Outcome measures
Measure	MLN2480 200 mg + Paclitaxel 80 mg/m^2 n=4 Participants Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Paclitaxel 80 mg/m^2 n=6 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 600 mg + Paclitaxel 80 mg/m^2 n=8 Participants Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Cetuximab 250 mg/m^2 n=6 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	MLN2480 600 mg + Cetuximab 250 mg/m^2 n=7 Participants Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	ML2480 300 mg + Irinotecan 180 mg/m^2 n=1 Participants Dose Escalation Phase: MLN2480 300 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	ML2480 400 mg + Irinotecan 180 mg/m^2 n=7 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	Dose Expansion: MLN2480 600 mg + Paclitaxel 80 mg/m^2 n=10 Participants Dose Expansion Phase: MLN2480 600 mg, tablets, orally, once per week on Days 2, 9, 16 and 23 of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, once on 1, 8, and 15 of a 28-day cycle for up to 12 cycles.	MLN2480 100 mg + MLN0128 2 mg n=4 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and MLN0128 2 mg, capsules, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles.	MLN2480 100 mg + Alisertib 30 mg n=3 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 160 mg + Alisertib 30 mg n=7 Participants Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 200 mg + Alisertib 30 mg n=3 Participants Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Alisertib 40 mg n=8 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 40 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Paclitaxel 80 mg/m^2 n=4 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 milligram per square meter (mg/m\^2), intravenous (IV) infusion, once weekly (QW) for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 160 mg + Paclitaxel 80 mg/m^2 n=3 Participants Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	4 Participants	6 Participants	8 Participants	6 Participants	7 Participants	1 Participants	7 Participants	10 Participants	4 Participants	3 Participants	7 Participants	3 Participants	8 Participants	4 Participants	3 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	2 Participants	3 Participants	4 Participants	2 Participants	3 Participants	0 Participants	4 Participants	7 Participants	2 Participants	1 Participants	5 Participants	1 Participants	3 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: From Day 1, Cycle 1 through 30 days after the last dose in Cycle 1 (up to 8 weeks)

Population: The DLT-evaluable population was defined as all participants in the dose escalation phase of the study who either experienced DLT during cycle 1, or completed at least 75% of the scheduled doses in cycle 1 without DLT.

DLT was defined using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 and included: any drug-related hematologic toxicity ≥Grade 4 with the exception of Grade 4 neutropenia \<7 days duration; Grade 3 or 4 neutropenia with fever \>38.5 degrees Celsius and/or infection or neutropenia requiring colony-stimulating factor OR non-hematologic DLTs that were any Grade 3, 4, or 5 toxicity with the following exceptions: Grade 3 nausea, vomiting, diarrhea, and dehydration occurring in a setting of inadequate treatment; inadequately treated hypersensitivity reactions; Grade 3 elevated transaminases or urine electrolyte abnormality ≤1 week in duration; Grade 3 serum electrolyte abnormality ≤72 hours in duration. DLTs also included: drug-related adverse experience that lead to a dose modification; unresolved drug-related toxicity resulted in delay in initiation of Cycle 2.

Outcome measures

Outcome measures
Measure	MLN2480 200 mg + Paclitaxel 80 mg/m^2 n=4 Participants Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Paclitaxel 80 mg/m^2 n=6 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 600 mg + Paclitaxel 80 mg/m^2 n=8 Participants Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Cetuximab 250 mg/m^2 n=6 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	MLN2480 600 mg + Cetuximab 250 mg/m^2 n=7 Participants Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	ML2480 300 mg + Irinotecan 180 mg/m^2 n=1 Participants Dose Escalation Phase: MLN2480 300 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	ML2480 400 mg + Irinotecan 180 mg/m^2 n=7 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	Dose Expansion: MLN2480 600 mg + Paclitaxel 80 mg/m^2 n=10 Participants Dose Expansion Phase: MLN2480 600 mg, tablets, orally, once per week on Days 2, 9, 16 and 23 of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, once on 1, 8, and 15 of a 28-day cycle for up to 12 cycles.	MLN2480 100 mg + MLN0128 2 mg n=4 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and MLN0128 2 mg, capsules, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles.	MLN2480 100 mg + Alisertib 30 mg n=3 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 160 mg + Alisertib 30 mg n=7 Participants Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 200 mg + Alisertib 30 mg n=3 Participants Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Alisertib 40 mg n=8 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 40 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Paclitaxel 80 mg/m^2 n=8 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 milligram per square meter (mg/m\^2), intravenous (IV) infusion, once weekly (QW) for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 160 mg + Paclitaxel 80 mg/m^2 n=3 Participants Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.
Number of Participants With Dose-Limiting Toxicities (DLTs)	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1, Cycle 1 up to 28 days

Outcome measures

Outcome measures
Measure	MLN2480 200 mg + Paclitaxel 80 mg/m^2 n=4 Participants Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Paclitaxel 80 mg/m^2 n=6 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 600 mg + Paclitaxel 80 mg/m^2 n=8 Participants Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 400 mg + Cetuximab 250 mg/m^2 n=6 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	MLN2480 600 mg + Cetuximab 250 mg/m^2 n=7 Participants Dose Escalation Phase: MLN2480 600 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and cetuximab administered intravenously at a loading dose of 400 mg/m\^2 (cycle 1 Day 1), then at 250 mg/m\^2 QW on Days 8, 15, and 22 of cycle 1 and Days 1, 8, 15, and 22 in each additional 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in cetuximab dose was based on the standard of care.	ML2480 300 mg + Irinotecan 180 mg/m^2 n=1 Participants Dose Escalation Phase: MLN2480 300 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	ML2480 400 mg + Irinotecan 180 mg/m^2 n=7 Participants Dose Escalation Phase: MLN2480 400 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and irinotecan 180 mg/m\^2, IV infusion over 90 minutes, every other week (Q2W) for 2 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in irinotecan dose was based on the standard of care.	Dose Expansion: MLN2480 600 mg + Paclitaxel 80 mg/m^2 n=10 Participants Dose Expansion Phase: MLN2480 600 mg, tablets, orally, once per week on Days 2, 9, 16 and 23 of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, once on 1, 8, and 15 of a 28-day cycle for up to 12 cycles.	MLN2480 100 mg + MLN0128 2 mg n=4 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and MLN0128 2 mg, capsules, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles.	MLN2480 100 mg + Alisertib 30 mg n=3 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 160 mg + Alisertib 30 mg n=7 Participants Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, twice daily (BID) on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 200 mg + Alisertib 30 mg n=3 Participants Dose Escalation Phase: MLN2480 200 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 30 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Alisertib 40 mg n=8 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and alisertib 40 mg, tablets, orally, BID on protocol specified days of a 28-day cycle for up to 12 cycles. The doses of MLN2480 and alisertib were modified during this phase based on tolerability during each 28-day cycle.	MLN2480 100 mg + Paclitaxel 80 mg/m^2 n=8 Participants Dose Escalation Phase: MLN2480 100 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 milligram per square meter (mg/m\^2), intravenous (IV) infusion, once weekly (QW) for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.	MLN2480 160 mg + Paclitaxel 80 mg/m^2 n=3 Participants Dose Escalation Phase: MLN2480 160 mg, tablets, orally, once on protocol specified days of a 28-day cycle for up to 12 cycles, and paclitaxel 80 mg/m\^2, IV infusion, QW for 3 weeks in each 28-day cycle for up to 12 cycles. The dose of MLN2480 was modified during this phase based on tolerability during each 28-day cycle. Any changes in paclitaxel dose was based on the standard of care.
Maximum Tolerated Dose (MTD) for MLN2480	NA mg MTD was not established.	NA mg MTD was not established.	600 mg	NA mg MTD was not established.	NA mg MTD was not established.	NA mg MTD was not established.	NA mg MTD was not established.	NA mg MTD was not established.	NA mg MTD was not established.	NA mg MTD was not established.	NA mg MTD was not established.	NA mg MTD was not established.	NA mg MTD was not established.	NA mg MTD was not established.	NA mg MTD was not established.

PRIMARY outcome

Timeframe: Day 1, Cycle 1 up to 28 days