Trial Outcomes & Findings for Nivolumab and Metformin Hydrochloride in Treating Patients With Stage III-IV Non-small Cell Lung Cancer That Cannot Be Removed by Surgery (NCT NCT03048500)

Last Updated: 2020-10-14

Results Overview

Anti-tumor activity will be assessed by ORR (defined as the sum of Complete Responses (CR) and/or Partial Responses (PR)) as measured by CT or MRI scan approximately every 8 weeks and assessed by Response Evaluation Criteria in Solid Tumors, RECIST criteria v1.1 using the patients best response to treatment where: CR=Disappearance of all lesions PR=At least a 30% decrease in the sum of the diameters of the target lesions, taking as reference the baseline sum diameters

Recruitment status

UNKNOWN

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

up to a maximum of 24 weeks from start of treatment (Range of cycles that best response was seen was 2-5 cycles of treatment where 1 cycle =28 days)

Results posted on

2020-10-14

Participant Flow

The first patient started treatment July 12, 2017. The study was designed to enroll patients with/without prior PD-1/PD-L1 inhibitor treatment. The study closed enrollment to patients without prior treatment with PD-1/PD-L1 inhibitor April 30, 2018. The study was suspended for IA and subsequently closed to further enrollment August 13, 2019.

Participant milestones

Participant milestones
Measure	Treatment (Metformin Hydrochloride, Nivolumab) Induction: Patients receive treatment with metformin monotherapy PO QD on Day -7 to -1. Main treatment starting Day 1 of Cycle 1: Patients receive metformin PO QD (Days 1-28 of a 28 days cycle) and nivolumab IV every 14 days (on Days 1 and 15 of a 28 day cycle) for the first 4 cycles and then every 28 days, starting Cycle 5 (Day 1 of a 28 day cycle). 28 day cycles continue in the absence of disease progression, unacceptable toxicity, or withdrawal of consent. Laboratory Biomarker Analysis: Correlative studies Metformin Hydrochloride: Given PO Nivolumab: Given IV
2 Cycles of Treatment STARTED	17
2 Cycles of Treatment Attempted 1st Cycle	17
2 Cycles of Treatment Attempted 2nd Cycle	16
2 Cycles of Treatment COMPLETED	16
2 Cycles of Treatment NOT COMPLETED	1
Reached 1st Response/Continued Treatment STARTED	16
Reached 1st Response/Continued Treatment Assessed for First Response	16
Reached 1st Response/Continued Treatment Went on to Cycle 3 and Beyond	9
Reached 1st Response/Continued Treatment COMPLETED	9
Reached 1st Response/Continued Treatment NOT COMPLETED	7
Follow up for 3 Years STARTED	16
Follow up for 3 Years COMPLETED	0
Follow up for 3 Years NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Metformin Hydrochloride, Nivolumab) Induction: Patients receive treatment with metformin monotherapy PO QD on Day -7 to -1. Main treatment starting Day 1 of Cycle 1: Patients receive metformin PO QD (Days 1-28 of a 28 days cycle) and nivolumab IV every 14 days (on Days 1 and 15 of a 28 day cycle) for the first 4 cycles and then every 28 days, starting Cycle 5 (Day 1 of a 28 day cycle). 28 day cycles continue in the absence of disease progression, unacceptable toxicity, or withdrawal of consent. Laboratory Biomarker Analysis: Correlative studies Metformin Hydrochloride: Given PO Nivolumab: Given IV
2 Cycles of Treatment Withdrawal by Subject	1
Reached 1st Response/Continued Treatment Progressive Disease	4
Reached 1st Response/Continued Treatment Death	1
Reached 1st Response/Continued Treatment Withdrawal by Subject	1
Reached 1st Response/Continued Treatment Physician decision, Patient PS declining	1
Follow up for 3 Years Currently in Follow-up	4
Follow up for 3 Years Death	12

Baseline Characteristics

Nivolumab and Metformin Hydrochloride in Treating Patients With Stage III-IV Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Metformin Hydrochloride, Nivolumab) n=17 Participants Induction: Patients receive treatment with metformin monotherapy PO QD on Day -7 to -1. Main treatment starting Day 1 of Cycle 1: Patients receive metformin PO QD (Days 1-28 of a 28 days cycle) and nivolumab IV every 14 days (on Days 1 and 15 of a 28 day cycle) for the first 4 cycles and then every 28 days, starting Cycle 5 (Day 1 of a 28 day cycle). 28 day cycles continue in the absence of disease progression, unacceptable toxicity, or withdrawal of consent. Laboratory Biomarker Analysis: Correlative studies Metformin Hydrochloride: Given PO Nivolumab: Given IV
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants

PRIMARY outcome

Timeframe: up to a maximum of 24 weeks from start of treatment (Range of cycles that best response was seen was 2-5 cycles of treatment where 1 cycle =28 days)

Population: All patients who received treatment are considered evaluable (even those who did not complete CT scans for RECIST measurement) except those removed from the study for adverse drug reactions.

Anti-tumor activity will be assessed by ORR (defined as the sum of Complete Responses (CR) and/or Partial Responses (PR)) as measured by CT or MRI scan approximately every 8 weeks and assessed by Response Evaluation Criteria in Solid Tumors, RECIST criteria v1.1 using the patients best response to treatment where: CR=Disappearance of all lesions PR=At least a 30% decrease in the sum of the diameters of the target lesions, taking as reference the baseline sum diameters

Outcome measures

Outcome measures
Measure	Treatment (Metformin Hydrochloride, Nivolumab) n=17 Participants Induction: Patients receive treatment with metformin monotherapy PO QD on Day -7 to -1. Main treatment starting Day 1 of Cycle 1: Patients receive metformin PO QD (Days 1-28 of a 28 days cycle) and nivolumab IV every 14 days (on Days 1 and 15 of a 28 day cycle) for the first 4 cycles and then every 28 days, starting Cycle 5 (Day 1 of a 28 day cycle). 28 day cycles continue in the absence of disease progression, unacceptable toxicity, or withdrawal of consent. Laboratory Biomarker Analysis: Correlative studies Metformin Hydrochloride: Given PO Nivolumab: Given IV
Objective Response Rate (ORR) of Patients With Non-small Cell Lung Cancer Treated With Nivolumab and Metformin Combination Using RECIST 1.1	1 Participants

SECONDARY outcome

Timeframe: 24 weeks from start of treatment

Depth of response (stable disease or partial response) defined as the change in the sum of the largest tumor diameters per RECIST v1.1 and irRECIST criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 3 years

Duration of response will be evaluated using RECIST v1.1 and irRECIST criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 3 years

Persistence of response will be assessed using RECIST v1.1 and irRECIST criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 weeks from start of treatment

DCR will be evaluated using RECIST v1.1 and irRECIST criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 1 year than at 2 years

PFS will be assessed using RECIST v1.1 and irRECIST criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 1 year than at 2 years

OS will be assessed using RECIST v1.1 and irRECIST criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to a maximum of 24 weeks from start of treatment (Range of cycles that best response was seen was 2-6 cycles of treatment where 1 cycle =28 days)

Anti-tumor activity will be assessed by ORR (defined as the sum of Complete Responses (CR) and/or Partial Responses (PR)) as measured by CT or MRI scan approximately every 8 weeks and assessed by irRECIST criteria using the patients best response to treatment where: CR=Disappearance of all lesions PR=At least a 30% decrease in the sum of the diameters of the target lesions, taking as reference the baseline sum diameters But also new measurable lesions are incorporated in the tumor burden, which is used to determine immune-related progressive disease (irPD), immune-related partial response (irPR), and immune-related complete response (irCR). New non-measurable lesions preclude irCR. Under RECST v1.1, there is no confirmation for PD. Under irRECIST, responses and irPDs must be confirmed by consecutive scans at least 4 weeks apart, assuming no clinical deterioration.

Outcome measures

Outcome measures
Measure	Treatment (Metformin Hydrochloride, Nivolumab) n=17 Participants Induction: Patients receive treatment with metformin monotherapy PO QD on Day -7 to -1. Main treatment starting Day 1 of Cycle 1: Patients receive metformin PO QD (Days 1-28 of a 28 days cycle) and nivolumab IV every 14 days (on Days 1 and 15 of a 28 day cycle) for the first 4 cycles and then every 28 days, starting Cycle 5 (Day 1 of a 28 day cycle). 28 day cycles continue in the absence of disease progression, unacceptable toxicity, or withdrawal of consent. Laboratory Biomarker Analysis: Correlative studies Metformin Hydrochloride: Given PO Nivolumab: Given IV
Objective Response Rate (ORR) of Patients With Non-small Cell Lung Cancer Treated With Nivolumab and Metformin Combination Using irRECIST.	2 Participants

SECONDARY outcome

Timeframe: Up to 3 years

Assess the safety and tolerability of the combination treatment of metformin with nivolumab by evaluating the number, frequency, and severity of adverse events using CTCAE version 4.03.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Metformin Hydrochloride, Nivolumab)

Serious events: 8 serious events

Other events: 17 other events

Deaths: 13 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Metformin Hydrochloride, Nivolumab) n=17 participants at risk Induction: Patients receive treatment with metformin monotherapy PO QD on Day -7 to -1. Main treatment starting Day 1 of Cycle 1: Patients receive metformin PO QD (Days 1-28 of a 28 days cycle) and nivolumab IV every 14 days (on Days 1 and 15 of a 28 day cycle) for the first 4 cycles and then every 28 days, starting Cycle 5 (Day 1 of a 28 day cycle). 28 day cycles continue in the absence of disease progression, unacceptable toxicity, or withdrawal of consent. Laboratory Biomarker Analysis: Correlative studies Metformin Hydrochloride: Given PO Nivolumab: Given IV
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease progression	11.8% 2/17 • Number of events 2 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small Cell Lung Cancer	5.9% 1/17 • Number of events 1 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Gastrointestinal disorders Constipation	5.9% 1/17 • Number of events 2 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.9% 1/17 • Number of events 1 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Cardiac disorders Pericardial effusion	5.9% 1/17 • Number of events 1 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Cardiac disorders Cardiac arrest and subsequent death	5.9% 1/17 • Number of events 1 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Infections and infestations Lung infection	5.9% 1/17 • Number of events 1 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Respiratory, thoracic and mediastinal disorders Hemoptysis and acute chronic obstructive pulmonary disease exacerbation	5.9% 1/17 • Number of events 1 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).

Other adverse events

Other adverse events
Measure	Treatment (Metformin Hydrochloride, Nivolumab) n=17 participants at risk Induction: Patients receive treatment with metformin monotherapy PO QD on Day -7 to -1. Main treatment starting Day 1 of Cycle 1: Patients receive metformin PO QD (Days 1-28 of a 28 days cycle) and nivolumab IV every 14 days (on Days 1 and 15 of a 28 day cycle) for the first 4 cycles and then every 28 days, starting Cycle 5 (Day 1 of a 28 day cycle). 28 day cycles continue in the absence of disease progression, unacceptable toxicity, or withdrawal of consent. Laboratory Biomarker Analysis: Correlative studies Metformin Hydrochloride: Given PO Nivolumab: Given IV
Blood and lymphatic system disorders Anemia	35.3% 6/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Cardiac disorders Cardiac arrest	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Cardiac disorders Sinus tachycardia	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Endocrine disorders Endocrine disorders - Other, specify	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Endocrine disorders Hypothyroidism	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Eye disorders Eye disorders - Other, specify	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Gastrointestinal disorders Abdominal distension	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Gastrointestinal disorders Constipation	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Gastrointestinal disorders Diarrhea	52.9% 9/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Gastrointestinal disorders Flatulence	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Gastrointestinal disorders Nausea	35.3% 6/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Gastrointestinal disorders Vomiting	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
General disorders Edema limbs	17.6% 3/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
General disorders Fatigue	41.2% 7/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
General disorders Fever	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
General disorders General disorders and administration site conditions - Other, specify	23.5% 4/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
General disorders Non-cardiac chest pain	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Infections and infestations Lung infection	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Infections and infestations Sinusitis	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Infections and infestations Urinary tract infection	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Injury, poisoning and procedural complications Fracture	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Investigations Alkaline phosphatase increased	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Investigations Aspartate aminotransferase increased	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Investigations INR increased	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Investigations Investigations - Other, specify	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Investigations Lymphocyte count decreased	41.2% 7/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Investigations Lymphocyte count increased	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Investigations Weight loss	47.1% 8/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Investigations White blood cell decreased	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Metabolism and nutrition disorders Anorexia	41.2% 7/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Metabolism and nutrition disorders Hypercalcemia	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Metabolism and nutrition disorders Hyperglycemia	29.4% 5/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Metabolism and nutrition disorders Hyperkalemia	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Metabolism and nutrition disorders Hypoalbuminemia	52.9% 9/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Metabolism and nutrition disorders Hypocalcemia	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Metabolism and nutrition disorders Hypokalemia	23.5% 4/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Metabolism and nutrition disorders Hypomagnesemia	17.6% 3/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Metabolism and nutrition disorders Hyponatremia	29.4% 5/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Metabolism and nutrition disorders Hypophosphatemia	35.3% 6/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Musculoskeletal and connective tissue disorders Back pain	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Musculoskeletal and connective tissue disorders Flank pain	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Musculoskeletal and connective tissue disorders Generalized muscle weakness	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	17.6% 3/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Musculoskeletal and connective tissue disorders Pain in extremity	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Nervous system disorders Dizziness	23.5% 4/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Nervous system disorders Headache	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Nervous system disorders Hypersomnia	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Nervous system disorders Memory impairment	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Nervous system disorders Nervous system disorders - Other, specify	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Nervous system disorders Paresthesia	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Nervous system disorders Peripheral motor neuropathy	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Psychiatric disorders Anxiety	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Psychiatric disorders Confusion	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Psychiatric disorders Depression	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Psychiatric disorders Insomnia	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Renal and urinary disorders Hematuria	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Renal and urinary disorders Proteinuria	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Renal and urinary disorders Renal and urinary disorders - Other, specify	11.8% 2/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Renal and urinary disorders Urinary frequency	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Respiratory, thoracic and mediastinal disorders Cough	17.6% 3/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Respiratory, thoracic and mediastinal disorders Dyspnea	23.5% 4/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Respiratory, thoracic and mediastinal disorders Productive cough	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	23.5% 4/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Respiratory, thoracic and mediastinal disorders Wheezing	5.9% 1/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Skin and subcutaneous tissue disorders Rash acneiform	17.6% 3/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	17.6% 3/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).
Vascular disorders Hypertension	58.8% 10/17 • Adverse events (AEs) were collected from Day -7 of Induction with Metformin until 30 days post the last dose of treatment (or at time of initiation of new treatment) for a maximum of 14 cycles for any patient (where 1 cycle = 28 days).

Additional Information

Young Chae, MD

Northwestern University

Phone: 312-695-1301

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place