Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin in People With Refractory Solid Tumors

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02723864
• Collaborator: (none)
• Enrollment: 53
• Locations: 3
• Arm: 1
• Actual Duration (Months): 52.7
• Patients Per Site: 17.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Background:

The drug cisplatin treats certain cancers when given with other chemotherapy drugs. Researchers think combining cisplatin with 2 other drugs could block proteins that support cancer cell growth. The other drugs are ABT-888 (veliparib) and M6620 (VX-970). They want to test if this drug combination slows the growth of cancer and is safe.

Objectives:

To test the safety and tolerability of VX-970 and veliparib combined with cisplatin in people with advanced refractory solid tumors. To determine the maximum tolerated dose of these drugs.

Eligibility:

People ages 18 and older with:

• Solid tumors that have progressed after treatment or for which no treatment exists

• Normal organ and marrow function

Design:

Participants will be screened with:

• Medical history

• Physical exam

• Computed tomography (CT) scan or magnetic resonance imaging (MRI)

• Blood and urine tests

Participants will get the study drugs in 3-week cycles:

• Cisplatin in a vein on 1 or 2 days

• VX-970 in a vein on 2 days

• Veliparib by mouth twice a day on 6 days

In each cycle, participants will have 5 physical exams and blood tests 5 times.

In some cycles, participants will have CT scans or MRIs.

In cycle 1, participants may have 2 tumor biopsies. A small piece of tissue is removed by needle.

Participants will keep a study diary. They will write when they take the drugs and if they have side effects.

Participants will stay in the study as long as they tolerate the drugs and their tumors are not getting worse.

Participants will have a phone call about a month after their last dose.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: Veliparib + VX-970 + Cisplatin	Phase 1

Detailed Description

Background:

• Ataxia-telangiectasia-related (ATR) protein kinase is central to the deoxyribonucleic acid (DNA) damage response and homologous recombination, activating a series of phosphorylation cascades, culminating in cell cycle arrest to allow time for deoxyribonucleic acid (DNA) repair. ATR additionally facilitates homologous recombination repair through modulation of the p53-replication protein A (p53-RPA) complex bound to single-stranded deoxyribonucleic acid (ssDNA) during the DNA repair process.

• Poly (ADP-ribose) polymerase-1 (PARP-1) plays a pivotal role in base-excision repair of single strand breaks formed either due to direct genotoxic stress or during the processing of double strand breaks. PARP also plays a role in alternative end joining, which may contribute to combination activity. PARP-1 binding to sites of DNA damage results in activation of its catalytic activity and generation of chains of poly (ADP-ribosyl)ated polymers, which serve as docking sites for recruitment of DNA repair proteins.

• Veliparib (ABT-888) is a potent PARP 1/2 inhibitor with clinical evidence of potentiation of antitumor activity in combination with cisplatin in breast cancer gene (BRCA) mutation carriers and patients with sporadic triple-negative breast cancer.

• M6620 (VX-970) is a potent ATR inhibitor, with half maximal inhibitory concentration (IC(50) of 20 nanomolar and antitumor activity across a broad range of cell lines in combination with DNA damaging agents. Preclinical studies show M6620 (VX-970) synergizes with cisplatin to induce DNA damage and antitumor activity. The addition of PARP inhibitor veliparib with ATR inhibitor M6620 (VX-970) allows for impairment of DNA repair, the induction of a BRCA null phenotype, and potentiation of the antitumor activity of cisplatin.

Primary Objective:

-To establish the safety, tolerability, and the maximum tolerated dose (MTD) of the combination of M6620 (VX-970) and veliparib in combination with cisplatin in patients with advanced refractory solid tumors

Secondary Objectives:

• To assess the effect of the combination of M6620 (VX-970), veliparib, and cisplatin on markers of DNA damage and apoptosis

• To assess antitumor activity of the combination

Exploratory Objective:

-To investigate tumor genomic alterations potentially associated with acquired resistance to the combination of M6620 (VX-970), veliparib, and cisplatin

Eligibility:

• Patients must have histologically confirmed solid tumors for which all standard therapy known to prolong survival has failed in the metastatic setting, or for which standard therapies do not exist

• Patients must have had no major surgery, radiation, or chemotherapy within 3 weeks prior to entering the study

• Patients must have adequate organ function

Study Design:

• Initially, M6620 (VX-970) will be administered intravenously on Days 2 and 9 of each 21-day cycle. Veliparib will be administered orally twice a day (every (q)12 hours +/- 1 hour) for Days 1-3 and 8-10 of each 21-day cycle. Cisplatin will be administered at 40 mg/m^2 intravenously on Day 1 (and Day 8 from dose level 3 (DL3) onwards) of each 21-day cycle.

• As of Amendment I (12/7/2017), patients who have been on study for at least 6 cycles may have cisplatin administration held or discontinued at the discretion of the Principal Investigator (PI), Dr. Chen, in recognition of the cumulative neurotoxicity seen with cisplatin treatment. If cisplatin is not administered during a cycle M6620 (VX-970) will be administered on Days 1 and 8 of that cycle.

• The escalation portion of the trial will follow a standard 3+3 design, whereby patients will be dose escalated in cohorts of 3 until dose-limiting toxicity is observed

• Once the maximum tolerated dose (MTD) is established, up to 15 additional patients will be enrolled to an expansion phase at the MTD. Mandatory tumor biopsies will be obtained in the expansion phase to assess pharmacodynamic (PD) endpoints

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Study of Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor in Combination With Cisplatin in Patients With Refractory Solid Tumors
• Actual Study Start Date: Aug 9, 2017
• Actual Primary Completion Date: Dec 15, 2020
• Actual Study Completion Date: Dec 31, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: M6620 (VX-970) M6620 will be administered intravenous (IV) on Days 2 and 9 of each 21-day cycle; Veliparib will be administered orally twice a day (BID) Days 1-3 and 8-10 of each cycle; Cisplatin will be administered at 40 mg/m^2 IV Day 1 (and Day 8 from dose level 3 onwards) of each cycle

Drug: Veliparib + VX-970 + Cisplatin; Ataxia-telangiectasia-related (ATR) protein kinase is central to the deoxyribonucleic acid (DNA) damage response and homologous recombination, activating a series of phosphorylation cascades, culminating in cell cycle arrest to allow time for DNA repair. Poly (ADP-ribose) polymerase (PARP) plays a pivotal role in base-excision repair of single strand breaks formed either due to direct genotoxic stress or during the processing of double strand breaks. Preclinical studies show ATR inhibitor M6620 (VX-970) synergizes with cisplatin to induce DNA damage and antitumor activity. The addition of PARP inhibitor veliparib with VX-970 allows for impairment of DNA repair, induction of a breast cancer gene (BRCA) null phenotype, and potentiation of the antitumor activity of cisplatin.; Other Names: ABT-888 + M6620 (berzosertib) + Cisplatinum

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Worst Grade 2 or Higher Adverse Events Occurring in >5% of Participants at Least Possibly Related to Study Drugs [Cycle 1 (i.e., one cycle = 21 days)]

   Adverse events were assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life threatening, and Grade 4 is life threatening.

Secondary Outcome Measures

1. Number of Participants With RAD51 Recombinase (Rad51), Phosphorylated Histone H2AX (γH2AX), Phosphorylated at Serine 343 (pS343)-Nibrin (Nbs1), and Phosphorylated KRAB-associated Protein 1 (pKAP-1) Induced After Treatment [Cycle 1 Day 1, and Cycle 1 Day 9 (i.e., one cycle = 21 days)]

   Biopsies were collected at Cycle 1 Day 1, and Cycle 1 Day 9 and markers Rad51, γH2AX, pS343-Nbs1, and pKAP-1 were measured for deoxyribonucleic acid (DNA) damage and apoptosis by immunofluorescence assays (IFA).

2. Number of Participants With a Best Response to the Antitumor Activity of Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin [4 cycles (i.e., one cycle = 21 days)]

   Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, and the appearance of one or more new lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Other Outcome Measures

1. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) [Date treatment consent signed to date off study, approximately 6 months and 20 days, 3 months and 17 days, 24 months and 13 days, 9 months and 8 days, 5 months and 18 days, 35 months and 20 days, and 5 months and 22 days for each Arm/Group respectively.]

   Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

• Patients must have histologically confirmed solid tumors for which standard therapy known to prolong survival has failed in the metastatic setting or for which standard therapies do not exist.

• Tumor amenable to biopsy and willingness to undergo tumor biopsies before and after M6620 (VX-970) treatment during the expansion phase of the trial (biopsies optional during the escalation phase).

• Patients must have completed any chemotherapy, radiation therapy, surgery, or biologic therapy greater than or equal to 3 weeks (or greater than or equal to 5 half-lives, whichever is shorter) prior to entering the study. Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in an exploratory investigational new drug (IND)/Phase 0 study and greater than or equal to 1 week since any palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events.

• Age greater than or equal to 18 years of age.

• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.

• Life expectancy > 3 months.

• Patients must have normal organ and marrow function as defined below:

• absolute neutrophil count greater than or equal to 1,500/mcL

• hemoglobin greater than or equal to 10 g/dL

• platelets greater than or equal to 100,000/mcL

• total bilirubin less than or equal to 1.5 X institutional upper limit of normal

• Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase(SGOT)/alanine aminotransferase (ALT) Serum glutamic pyruvic transaminase (SGPT) less than or equal to 1.5 X institutional upper limit of normal (OR < 3X upper limit of normal (ULN) in the setting of liver metastases)

• creatinine less than or equal to 1.5X institutional upper limit of normal

OR

• creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• The effects of M6620 (VX-970) and veliparib on the developing human fetus are unknown. For this reason and because cisplatin is known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after completing study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after completion of administration of study agents.

• Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with M6620 (VX-970). In addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy.

• Patients must be able to swallow whole tablets or capsules. Nasogastric or gastric (G)-tube administration is not allowed. Any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed.

• Ability to understand and the willingness to sign a written informed consent document.

• During the expansion phase of the protocol, patients must have disease amenable to biopsy and be willing to undergo pre- and post-treatment biopsies.

• Patients must have greater than or equal to 10.0 g/dL hemoglobin (Hb) and no blood transfusion in the past 28 days to receive Veliparib.

EXCLUSION CRITERIA:

• Patients who are receiving any other investigational agents.

• Patients with known active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients whose brain metastatic disease status has remained stable for greater than or equal to 4 weeks following treatment of brain metastases are eligible to participate at the discretion of the principal investigator.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active untreated infection, or psychiatric illness/social situations that would limit compliance with study requirements.

• Patients required to be on any of the concomitant medications are excluded.

• Pregnant women and women who are breastfeeding are excluded from this study because the effects of the study drugs on the developing fetus are unknown.

• Patients who have had prior platinum-based therapy who have > Grade 1 neurotoxicity or ototoxicity at the time of enrollment will not be permitted on study.

• Patients with a seizure history will not be permitted on protocol due to association of veliparib with seizure activity in animal toxicology studies at higher doses. Patients on anticonvulsant medications will not be permitted on study due to the potential to lower plasma levels of anticonvulsants and risk for seizure activity.

• Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/Myelodysplastic syndromes (MDS), or with features suggestive of AML/MDS, or who have had prior allogeneic bone marrow transplant or double umbilical cord blood transplantation, should not receive Veliparib due to reports of MDS and leukemia secondary to oncology therapy on Cancer Therapy Evaluation Program (CTEP)-sponsored studies utilizing Veliparib.

INCLUSION of WOMEN and MINORITIES

Both men and women of all races and ethnic groups are eligible for this trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
3	MD Anderson Cancer Center	Houston	Texas	United States	77030-4096

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Alice P Chen, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 11, 2021
• Informed Consent Form - Jan 11, 2021

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Chen X, Wu Y, Dong H, Zhang CY, Zhang Y. Platinum-based agents for individualized cancer treatment. Curr Mol Med. 2013 Dec;13(10):1603-12. Review.
• Donawho CK, Luo Y, Luo Y, Penning TD, Bauch JL, Bouska JJ, Bontcheva-Diaz VD, Cox BF, DeWeese TL, Dillehay LE, Ferguson DC, Ghoreishi-Haack NS, Grimm DR, Guan R, Han EK, Holley-Shanks RR, Hristov B, Idler KB, Jarvis K, Johnson EF, Kleinberg LR, Klinghofer V, Lasko LM, Liu X, Marsh KC, McGonigal TP, Meulbroek JA, Olson AM, Palma JP, Rodriguez LE, Shi Y, Stavropoulos JA, Tsurutani AC, Zhu GD, Rosenberg SH, Giranda VL, Frost DJ. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res. 2007 May 1;13(9):2728-37.
• Huntoon CJ, Flatten KS, Wahner Hendrickson AE, Huehls AM, Sutor SL, Kaufmann SH, Karnitz LM. ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status. Cancer Res. 2013 Jun 15;73(12):3683-91. doi: 10.1158/0008-5472.CAN-13-0110. Epub 2013 Apr 2.

• Responsible Party: Alice Chen, M.D., Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02723864
• Other Study ID Numbers: 160087; 16-C-0087
• First Posted: Mar 31, 2016
• Last Update Posted: Feb 8, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alice Chen, M.D., Principal Investigator, National Cancer Institute (NCI): Pharmacodynamic; DNA Damage Repair; BRCA Null; Apoptosis; Combination Therapy
• Additional relevant MeSH terms: Veliparib

Study Results

Participant Flow

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4	Dose Level 5	Dose Level 6	Dose Level 7
Arm/Group Description	DL 1: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 90 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 2: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 140 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 3: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 120 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 4: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 5: ABT-888 150 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 6: ABT-888 200 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 7: ABT-888 300 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 IV over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 intravenous (IV) over 1hr days 1 & 8 (optional after 6 cycles)
Period Title: Overall Study
STARTED	3	3	6	7	3	25	6
COMPLETED	2	2	5	7	2	14	4
NOT COMPLETED	1	1	1	0	1	11	2

Baseline Characteristics

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4	Dose Level 5	Dose Level 6	Dose Level 7	Total
Arm/Group Description	DL 1: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 90 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 2: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 140 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 3: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 120 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 4: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 5: ABT-888 150 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 6: ABT-888 200 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 7: ABT-888 300 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 IV over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 intravenous (IV) over 1hr days 1 & 8 (optional after 6 cycles)	Total of all reporting groups
Overall Participants	3	3	6	7	3	25	6	53
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 66.7%	2 66.7%	6 100%	5 71.4%	3 100%	20 80%	6 100%	44 83%
>=65 years	1 33.3%	1 33.3%	0 0%	2 28.6%	0 0%	5 20%	0 0%	9 17%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.67 (7.64)	51 (15.39)	54.83 (10.65)	57.86 (13.21)	58 (5.57)	53.4 (14.28)	44.83 (14.3)	53.6 (13.11)
Sex: Female, Male (Count of Participants)
Female	0 0%	2 66.7%	6 100%	5 71.4%	1 33.3%	9 36%	4 66.7%	27 50.9%
Male	3 100%	1 33.3%	0 0%	2 28.6%	2 66.7%	16 64%	2 33.3%	26 49.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	3 12%	0 0%	3 5.7%
Not Hispanic or Latino	3 100%	3 100%	6 100%	7 100%	2 66.7%	21 84%	6 100%	48 90.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	1 33.3%	1 4%	0 0%	2 3.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 16.7%	3 42.9%	1 33.3%	3 12%	0 0%	8 15.1%
White	3 100%	3 100%	5 83.3%	4 57.1%	2 66.7%	19 76%	6 100%	42 79.2%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	3 12%	0 0%	3 5.7%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	6 100%	7 100%	3 100%	25 100%	6 100%	53 100%
Eastern Cooperative Oncology Performance Status (ECOG) (Count of Participants)
ECOG 0	0 0%	0 0%	2 33.3%	0 0%	0 0%	5 20%	2 33.3%	9 17%
ECOG 1	2 66.7%	3 100%	4 66.7%	7 100%	3 100%	19 76%	4 66.7%	42 79.2%
ECOG 2	1 33.3%	0 0%	0 0%	0 0%	0 0%	1 4%	0 0%	2 3.8%
Diagnosis: Tumor Type (Count of Participants)
Lung cancer	0 0%	0 0%	0 0%	0 0%	0 0%	1 4%	1 16.7%	2 3.8%
Ovarian cancer	0 0%	1 33.3%	2 33.3%	1 14.3%	0 0%	2 8%	0 0%	6 11.3%
Liver cancer	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Uterine cancer	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	1 1.9%
Pancreatic cancer	2 66.7%	0 0%	0 0%	0 0%	0 0%	3 12%	0 0%	5 9.4%
Peritoneal cancer	0 0%	0 0%	0 0%	0 0%	0 0%	1 4%	0 0%	1 1.9%
Breast cancer	0 0%	0 0%	2 33.3%	0 0%	0 0%	1 4%	0 0%	3 5.7%
Colon cancer	0 0%	0 0%	1 16.7%	0 0%	0 0%	2 8%	0 0%	3 5.7%
Esophageal cancer	0 0%	0 0%	0 0%	1 14.3%	0 0%	1 4%	0 0%	2 3.8%
Other	1 33.3%	2 66.7%	1 16.7%	5 71.4%	3 100%	14 56%	4 66.7%	30 56.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Worst Grade 2 or Higher Adverse Events Occurring in >5% of Participants at Least Possibly Related to Study Drugs
Description	Adverse events were assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life threatening, and Grade 4 is life threatening.
Time Frame	Cycle 1 (i.e., one cycle = 21 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Grade 2 Adverse Events - Dose Level 1	Grade 3 Adverse Events - Dose Level 1	Grade 4 Adverse Events - Dose Level 1	Grade 2 Adverse Events - Dose Level 2	Grade 3 Adverse Events - Dose Level 2	Grade 4 Adverse Events - Dose Level 2	Grade 2 Adverse Events - Dose Level 3	Grade 3 Adverse Events - Dose Level 3	Grade 4 Adverse Events - Dose Level 3	Grade 2 Adverse Events - Dose Level 4	Grade 3 Adverse Events - Dose Level 4	Grade 4 Adverse Events - Dose Level 4	Grade 2 Adverse Events - Dose Level 5	Grade 3 Adverse Events - Dose Level 5	Grade 4 Adverse Events - Dose Level 5	Grade 2 Adverse Events - Dose Level 6	Grade 3 Adverse Events - Dose Level 6	Grade 4 Adverse Events - Dose Level 6	Grade 2 Adverse Events - Dose Level 7	Grade 3 Adverse Events - Dose Level 7	Grade 4 Adverse Events - Dose Level 7
Arm/Group Description	DL 1: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 90 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 1: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 90 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 1: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 90 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 2: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 140 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 2: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 140 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 2: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 140 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 3: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 120 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 3: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 120 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 3: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 120 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 4: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 4: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 4: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 5: ABT-888 150 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 5: ABT-888 150 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 5: ABT-888 150 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 6: ABT-888 200 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 6: ABT-888 200 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 6: ABT-888 200 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 7: ABT-888 300 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 IV over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 intravenous (IV) over 1hr days 1 & 8 (optional after 6 cycles)	DL 7: ABT-888 300 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 IV over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 intravenous (IV) over 1hr days 1 & 8 (optional after 6 cycles)	DL 7: ABT-888 300 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 IV over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 intravenous (IV) over 1hr days 1 & 8 (optional after 6 cycles)
Measure Participants	3	3	3	3	3	3	6	6	6	7	7	7	3	3	3	25	25	25	6	6	6
Alkaline phosphatase increased	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Anemia	1 33.3%	1 33.3%	0 0%	0 0%	0 0%	0 0%	3 50%	3 5.7%	0 NaN	3 NaN	3 NaN	0 NaN	0 NaN	3 NaN	0 NaN	6 NaN	10 NaN	1 NaN	1 NaN	2 NaN	0 NaN
Creatinine increased	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	3 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Fatigue	2 66.7%	0 0%	0 0%	2 28.6%	0 0%	0 0%	2 33.3%	0 0%	0 NaN	1 NaN	0 NaN	0 NaN	2 NaN	0 NaN	0 NaN	3 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Hypertension	2 66.7%	0 0%	0 0%	0 0%	0 0%	0 0%	3 50%	1 1.9%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	4 NaN	5 NaN	0 NaN	1 NaN	1 NaN	0 NaN
Hypomagnesemia	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	2 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Hyponatremia	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.9%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Hypophosphatemia	1 33.3%	1 33.3%	0 0%	2 28.6%	0 0%	0 0%	2 33.3%	1 1.9%	0 NaN	1 NaN	1 NaN	0 NaN	1 NaN	0 NaN	0 NaN	2 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Infusion related reaction	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	2 NaN	1 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Lymphocyte count decreased	0 0%	2 66.7%	0 0%	1 14.3%	1 33.3%	0 0%	1 16.7%	1 1.9%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	2 NaN	4 NaN	1 NaN	1 NaN	0 NaN	0 NaN
Nausea	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	4 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Neutrophil count decreased	1 33.3%	0 0%	0 0%	2 28.6%	0 0%	0 0%	2 33.3%	2 3.8%	0 NaN	1 NaN	2 NaN	0 NaN	1 NaN	0 NaN	0 NaN	3 NaN	2 NaN	0 NaN	0 NaN	3 NaN	1 NaN
Peripheral sensory neuropathy	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 33.3%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	2 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Platelet count decreased	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 3.8%	0 NaN	1 NaN	3 NaN	1 NaN	0 NaN	2 NaN	0 NaN	2 NaN	4 NaN	3 NaN	1 NaN	1 NaN	1 NaN
Proteinuria	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Thromboembolic event	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.9%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN	4 NaN	0 NaN	0 NaN	0 NaN	0 NaN
White blood cell decreased	1 33.3%	0 0%	0 0%	2 28.6%	0 0%	0 0%	0 0%	2 3.8%	0 NaN	0 NaN	3 NaN	0 NaN	0 NaN	1 NaN	0 NaN	4 NaN	4 NaN	1 NaN	1 NaN	2 NaN	0 NaN

2. Secondary Outcome

Title	Number of Participants With RAD51 Recombinase (Rad51), Phosphorylated Histone H2AX (γH2AX), Phosphorylated at Serine 343 (pS343)-Nibrin (Nbs1), and Phosphorylated KRAB-associated Protein 1 (pKAP-1) Induced After Treatment
Description	Biopsies were collected at Cycle 1 Day 1, and Cycle 1 Day 9 and markers Rad51, γH2AX, pS343-Nbs1, and pKAP-1 were measured for deoxyribonucleic acid (DNA) damage and apoptosis by immunofluorescence assays (IFA).
Time Frame	Cycle 1 Day 1, and Cycle 1 Day 9 (i.e., one cycle = 21 days)

Outcome Measure Data

Analysis Population Description

These measurements were only carried out on the subset (7/25) of DL6 participants from whom evaluable C1D1 and C1D9 biopsies were collected.

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4	Dose Level 5	Dose Level 6	Dose Level 7
Arm/Group Description	DL 1: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 90 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 2: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 140 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 3: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 120 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 4: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 5: ABT-888 150 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 6: ABT-888 200 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 7: ABT-888 300 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 IV over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 intravenous (IV) over 1hr days 1 & 8 (optional after 6 cycles)
Measure Participants	0	0	0	0	0	7	0
Rad51 induced after veliparib and cisplatin treatment on Cycle 1, Day 1	5 166.7%
Rad51 induced after veliparib, cisplatin and M6620 treatment on Cycle 1, Day 9	5 166.7%
γH2AX induced after veliparib and cisplatin treatment on Cycle 1, Day 1	0 0%
γH2AX induced after veliparib, cisplatin and M6620 treatment on Cycle 1, Day 9	0 0%
pS343-Nbs1 induced after veliparib and cisplatin treatment on Cycle 1, Day 1	1 33.3%
pS343-Nbs1 induced after veliparib, cisplatin and M6620 treatment on Cycle 1, Day 9	0 0%
pKap1 induced after veliparib and cisplatin treatment on Cycle 1, Day 1	0 0%
pKap1 induced after veliparib, cisplatin and M6620 treatment on Cycle 1, Day 9	0 0%

3. Secondary Outcome

Title	Number of Participants With a Best Response to the Antitumor Activity of Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin
Description	Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, and the appearance of one or more new lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame	4 cycles (i.e., one cycle = 21 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4	Dose Level 5	Dose Level 6	Dose Level 7
Arm/Group Description	DL 1: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 90 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 2: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 140 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 3: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 120 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 4: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 5: ABT-888 150 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 6: ABT-888 200 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 7: ABT-888 300 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 IV over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 intravenous (IV) over 1hr days 1 & 8 (optional after 6 cycles)
Measure Participants	3	3	6	7	3	25	6
Complete Response	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Partial Response	0 0%	0 0%	2 33.3%	0 0%	0 0%	3 12%	0 0%
Stable Disease	1 33.3%	2 66.7%	3 50%	4 57.1%	3 100%	10 40%	3 50%
Progressive Disease	2 66.7%	1 33.3%	1 16.7%	3 42.9%	0 0%	5 20%	3 50%
Not Evaluable for Response	0 0%	0 0%	0 0%	0 0%	0 0%	7 28%	0 0%

4. Other Pre-specified Outcome

Title	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Description	Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame	Date treatment consent signed to date off study, approximately 6 months and 20 days, 3 months and 17 days, 24 months and 13 days, 9 months and 8 days, 5 months and 18 days, 35 months and 20 days, and 5 months and 22 days for each Arm/Group respectively.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4	Dose Level 5	Dose Level 6	Dose Level 7
Arm/Group Description	DL 1: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 90 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 2: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 140 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)	DL 3: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 120 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 4: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 5: ABT-888 150 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 6: ABT-888 200 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)	DL 7: ABT-888 300 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 IV over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 intravenous (IV) over 1hr days 1 & 8 (optional after 6 cycles)
Measure Participants	3	3	6	7	3	25	6
Count of Participants [Participants]	3 100%	3 100%	6 100%	7 100%	3 100%	25 100%	6 100%

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately 6 months and 20 days, 3 months and 17 days, 24 months and 13 days, 9 months and 8 days, 5 months and 18 days, 35 months and 20 days, and 5 months and 22 days for each Arm/Group respectively.
Arm/Group Title	Dose Level 1		Dose Level 2		Dose Level 3		Dose Level 4		Dose Level 5		Dose Level 6		Dose Level 7
Arm/Group Description	DL 1: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 90 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)		DL 2: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 140 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr day 1 (optional after 6 cycles)		DL 3: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 120 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)		DL 4: ABT-888 100 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)		DL 5: ABT-888 150 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)		DL 6: ABT-888 200 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 intravenous (IV) over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 IV over 1hr days 1 & 8 (optional after 6 cycles)		DL 7: ABT-888 300 mg by mouth (PO) every (Q)12 hours on days 1-3 & 8-10, VX-970 210 mg/m^2 IV over 1 hour days 2 & 9, Cisplatin 40 mg/m^2 intravenous (IV) over 1hr days 1 & 8 (optional after 6 cycles)
All Cause Mortality
	Dose Level 1		Dose Level 2		Dose Level 3		Dose Level 4		Dose Level 5		Dose Level 6		Dose Level 7
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/6 (0%)		0/7 (0%)		0/3 (0%)		1/25 (4%)		0/6 (0%)
Serious Adverse Events
	Dose Level 1		Dose Level 2		Dose Level 3		Dose Level 4		Dose Level 5		Dose Level 6		Dose Level 7
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		2/7 (28.6%)		1/3 (33.3%)		14/25 (56%)		0/6 (0%)
Blood and lymphatic system disorders
Anemia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	1/3 (33.3%)	1	5/25 (20%)	5	0/6 (0%)	0
Cardiac disorders
Pericardial effusion	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Pericardial tamponade	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Right ventricular dysfunction	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Eye disorders
Blurred vision	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/25 (0%)	0	0/6 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/25 (0%)	0	0/6 (0%)	0
Constipation	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Diarrhea	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Gastric ulcer	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
General disorders
Edema limbs	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Fever	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	1/25 (4%)	1	0/6 (0%)	0
Pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Hepatobiliary disorders
Bile duct stenosis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Infections and infestations
Catheter related infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	2	0/25 (0%)	0	0/6 (0%)	0
Infections and infestations - Other, Sepsis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	2	0/6 (0%)	0
Sepsis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	2	0/6 (0%)	0
Urinary tract infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	2	0/6 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Injury, poisoning and procedural complications - Other, fall	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Injury, poisoning and procedural complications - Other, hip fracture	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Investigations
Alanine aminotransferase increased	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Neutrophil count decreased	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Platelet count decreased	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	2/25 (8%)	3	0/6 (0%)	0
White blood cell decreased	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Metabolism and nutrition disorders
Hypokalemia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Hyponatremia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	1/25 (4%)	1	0/6 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, progressive disease	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Nervous system disorders
Syncope	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Psychiatric disorders
Confusion	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/25 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Hypoxia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Pleural effusion	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Pulmonary hypertension	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Vascular disorders
Hypotension	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Thromboembolic event	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	3/25 (12%)	3	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	Dose Level 1		Dose Level 2		Dose Level 3		Dose Level 4		Dose Level 5		Dose Level 6		Dose Level 7
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		6/6 (100%)		7/7 (100%)		3/3 (100%)		25/25 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Anemia	3/3 (100%)	9	3/3 (100%)	4	6/6 (100%)	57	6/7 (85.7%)	35	3/3 (100%)	21	19/25 (76%)	81	4/6 (66.7%)	19
Cardiac disorders
Atrial fibrillation	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Electrocardiogram QT corrected interval prolonged	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Palpitations	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Pericardial effusion	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	1/6 (16.7%)	1
Pericarditis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	1/6 (16.7%)	1
Sinus bradycardia	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	3	2/7 (28.6%)	2	0/3 (0%)	0	2/25 (8%)	2	1/6 (16.7%)	1
Sinus tachycardia	0/3 (0%)	0	1/3 (33.3%)	1	2/6 (33.3%)	20	1/7 (14.3%)	1	0/3 (0%)	0	11/25 (44%)	25	3/6 (50%)	4
Ear and labyrinth disorders
Ear pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Hearing impaired	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	3	0/3 (0%)	0	2/25 (8%)	3	0/6 (0%)	0
Tinnitus	0/3 (0%)	0	0/3 (0%)	0	3/6 (50%)	3	2/7 (28.6%)	2	0/3 (0%)	0	2/25 (8%)	2	1/6 (16.7%)	1
Eye disorders
Dry eye	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Eye disorders - Other, Sty	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Eye pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/25 (0%)	0	0/6 (0%)	0
Floaters	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Vitreous hemorrhage	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/3 (0%)	0	1/3 (33.3%)	1	1/6 (16.7%)	2	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	2	0/6 (0%)	0
Abdominal pain	0/3 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	3	1/7 (14.3%)	1	1/3 (33.3%)	1	5/25 (20%)	7	2/6 (33.3%)	2
Anal fistula	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/25 (0%)	0	0/6 (0%)	0
Anal hemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/25 (0%)	0	0/6 (0%)	0
Ascites	0/3 (0%)	0	1/3 (33.3%)	1	2/6 (33.3%)	3	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Bloating	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	3/25 (12%)	3	0/6 (0%)	0
Constipation	3/3 (100%)	4	1/3 (33.3%)	2	2/6 (33.3%)	5	3/7 (42.9%)	4	0/3 (0%)	0	11/25 (44%)	15	3/6 (50%)	3
Diarrhea	2/3 (66.7%)	3	1/3 (33.3%)	1	1/6 (16.7%)	6	3/7 (42.9%)	3	1/3 (33.3%)	2	11/25 (44%)	24	0/6 (0%)	0
Dry mouth	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Dyspepsia	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	2	1/7 (14.3%)	1	0/3 (0%)	0	2/25 (8%)	2	1/6 (16.7%)	1
Dysphagia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Fecal incontinence	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Gastritis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Gastroesophageal reflux disease	1/3 (33.3%)	1	0/3 (0%)	0	2/6 (33.3%)	2	0/7 (0%)	0	0/3 (0%)	0	4/25 (16%)	4	0/6 (0%)	0
Gastrointestinal disorders - Other, Cramping abdominal discomfort	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Hemorrhoidal hemorrhage	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Hemorrhoids	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	2	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Mucositis oral	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Nausea	1/3 (33.3%)	2	2/3 (66.7%)	2	3/6 (50%)	7	4/7 (57.1%)	4	1/3 (33.3%)	1	14/25 (56%)	17	2/6 (33.3%)	2
Oral hemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Oral pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Toothache	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Vomiting	1/3 (33.3%)	2	0/3 (0%)	0	2/6 (33.3%)	4	2/7 (28.6%)	2	0/3 (0%)	0	8/25 (32%)	14	0/6 (0%)	0
General disorders
Chills	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	4	0/6 (0%)	0
Edema face	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Edema limbs	0/3 (0%)	0	0/3 (0%)	0	4/6 (66.7%)	10	1/7 (14.3%)	1	0/3 (0%)	0	5/25 (20%)	7	0/6 (0%)	0
Facial pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Fatigue	3/3 (100%)	5	3/3 (100%)	5	4/6 (66.7%)	6	4/7 (57.1%)	7	2/3 (66.7%)	4	13/25 (52%)	16	5/6 (83.3%)	7
Fever	1/3 (33.3%)	1	1/3 (33.3%)	1	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	4/25 (16%)	6	0/6 (0%)	0
Flu like symptoms	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	1/3 (33.3%)	1	0/25 (0%)	0	0/6 (0%)	0
Gait disturbance	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Injection site reaction	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Localized edema	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	1/6 (16.7%)	2
Malaise	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	2/25 (8%)	3	0/6 (0%)	0
Pain	2/3 (66.7%)	2	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	3/25 (12%)	4	0/6 (0%)	0
Immune system disorders
Cytokine release syndrome	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Infections and infestations
Eye infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	1/25 (4%)	1	0/6 (0%)	0
Infections and infestations - Other, c diff infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Lip infection	0/3 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	3	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Lung infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	1/25 (4%)	1	0/6 (0%)	0
Phlebitis infective	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Skin infection	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Tooth infection	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Upper respiratory infection	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	3	0/6 (0%)	0
Urinary tract infection	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	1/6 (16.7%)	2
Injury, poisoning and procedural complications
Bruising	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Fall	0/3 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	2	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	3	0/6 (0%)	0
Infusion related reaction	1/3 (33.3%)	1	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	3/25 (12%)	4	2/6 (33.3%)	3
Injury, poisoning and procedural complications - Other, head injury	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	1/3 (33.3%)	1	1/25 (4%)	1	0/6 (0%)	0
Alanine aminotransferase increased	1/3 (33.3%)	1	1/3 (33.3%)	2	3/6 (50%)	5	1/7 (14.3%)	5	0/3 (0%)	0	4/25 (16%)	4	2/6 (33.3%)	3
Alkaline phosphatase increased	1/3 (33.3%)	2	0/3 (0%)	0	3/6 (50%)	6	2/7 (28.6%)	7	1/3 (33.3%)	1	3/25 (12%)	4	1/6 (16.7%)	1
Aspartate aminotransferase increased	1/3 (33.3%)	1	1/3 (33.3%)	1	2/6 (33.3%)	3	2/7 (28.6%)	5	1/3 (33.3%)	2	7/25 (28%)	7	4/6 (66.7%)	5
Blood bilirubin increased	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	2/7 (28.6%)	4	0/3 (0%)	0	2/25 (8%)	2	0/6 (0%)	0
Creatinine increased	1/3 (33.3%)	1	1/3 (33.3%)	1	4/6 (66.7%)	6	3/7 (42.9%)	5	0/3 (0%)	0	6/25 (24%)	18	0/6 (0%)	0
Investigations - Other, hyponatremia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Investigations - Other, LDH Inc	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	3/25 (12%)	5	0/6 (0%)	0
Lymphocyte count decreased	2/3 (66.7%)	17	2/3 (66.7%)	10	2/6 (33.3%)	12	1/7 (14.3%)	7	1/3 (33.3%)	4	9/25 (36%)	74	1/6 (16.7%)	2
Neutrophil count decreased	1/3 (33.3%)	2	2/3 (66.7%)	5	5/6 (83.3%)	15	4/7 (57.1%)	12	1/3 (33.3%)	2	7/25 (28%)	56	5/6 (83.3%)	12
Platelet count decreased	2/3 (66.7%)	6	3/3 (100%)	5	4/6 (66.7%)	13	7/7 (100%)	27	2/3 (66.7%)	13	17/25 (68%)	62	5/6 (83.3%)	17
Weight loss	0/3 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	3	0/7 (0%)	0	0/3 (0%)	0	4/25 (16%)	5	0/6 (0%)	0
White blood cell decreased	1/3 (33.3%)	7	2/3 (66.7%)	8	2/6 (33.3%)	15	5/7 (71.4%)	20	2/3 (66.7%)	11	11/25 (44%)	81	4/6 (66.7%)	15
Metabolism and nutrition disorders
Anorexia	0/3 (0%)	0	1/3 (33.3%)	1	4/6 (66.7%)	6	2/7 (28.6%)	3	2/3 (66.7%)	2	9/25 (36%)	11	0/6 (0%)	0
Dehydration	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	4/25 (16%)	6	0/6 (0%)	0
Hypercalcemia	1/3 (33.3%)	2	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Hyperglycemia	3/3 (100%)	4	1/3 (33.3%)	1	1/6 (16.7%)	1	2/7 (28.6%)	6	1/3 (33.3%)	12	14/25 (56%)	25	3/6 (50%)	6
Hyperkalemia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	3/25 (12%)	9	0/6 (0%)	0
Hypermagnesemia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Hypoalbuminemia	1/3 (33.3%)	2	2/3 (66.7%)	2	1/6 (16.7%)	4	1/7 (14.3%)	2	2/3 (66.7%)	4	8/25 (32%)	23	1/6 (16.7%)	1
Hypocalcemia	2/3 (66.7%)	3	0/3 (0%)	0	2/6 (33.3%)	6	0/7 (0%)	0	0/3 (0%)	0	5/25 (20%)	12	0/6 (0%)	0
Hypoglycemia	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Hypokalemia	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/7 (14.3%)	1	1/3 (33.3%)	2	5/25 (20%)	10	0/6 (0%)	0
Hypomagnesemia	2/3 (66.7%)	4	2/3 (66.7%)	5	4/6 (66.7%)	10	3/7 (42.9%)	6	1/3 (33.3%)	1	8/25 (32%)	32	3/6 (50%)	6
Hyponatremia	2/3 (66.7%)	4	2/3 (66.7%)	4	3/6 (50%)	8	2/7 (28.6%)	8	2/3 (66.7%)	4	11/25 (44%)	24	4/6 (66.7%)	6
Hypophosphatemia	2/3 (66.7%)	8	2/3 (66.7%)	3	3/6 (50%)	7	2/7 (28.6%)	7	1/3 (33.3%)	1	6/25 (24%)	13	1/6 (16.7%)	1
Metabolism and nutrition disorders - Other, hyponatremia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	3	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Back pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	2/3 (66.7%)	2	2/25 (8%)	2	1/6 (16.7%)	2
Flank pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	2	0/6 (0%)	0
Generalized muscle weakness	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	2	0/25 (0%)	0	0/6 (0%)	0
Joint range of motion decreased	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Myalgia	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/7 (14.3%)	1	1/3 (33.3%)	1	0/25 (0%)	0	0/6 (0%)	0
Non-cardiac chest pain	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	2	2/25 (8%)	2	1/6 (16.7%)	1
Pain in extremity	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	3/7 (42.9%)	3	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Trismus	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	0/3 (0%)	0	1/3 (33.3%)	3	1/6 (16.7%)	1	1/7 (14.3%)	1	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Nervous system disorders
Dizziness	1/3 (33.3%)	2	2/3 (66.7%)	2	1/6 (16.7%)	2	1/7 (14.3%)	2	0/3 (0%)	0	4/25 (16%)	5	1/6 (16.7%)	1
Dysgeusia	0/3 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	2	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Headache	1/3 (33.3%)	1	1/3 (33.3%)	2	3/6 (50%)	4	3/7 (42.9%)	3	1/3 (33.3%)	1	4/25 (16%)	5	0/6 (0%)	0
Paresthesia	1/3 (33.3%)	1	1/3 (33.3%)	2	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Peripheral motor neuropathy	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Peripheral sensory neuropathy	0/3 (0%)	0	0/3 (0%)	0	3/6 (50%)	6	1/7 (14.3%)	1	0/3 (0%)	0	5/25 (20%)	5	1/6 (16.7%)	1
Psychiatric disorders
Anxiety	1/3 (33.3%)	1	1/3 (33.3%)	1	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	2	0/6 (0%)	0
Depression	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Insomnia	2/3 (66.7%)	4	3/3 (100%)	3	1/6 (16.7%)	1	1/7 (14.3%)	2	1/3 (33.3%)	1	6/25 (24%)	8	1/6 (16.7%)	1
Irritability	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	0/25 (0%)	0	0/6 (0%)	0
Mania	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Renal and urinary disorders
Cystitis noninfective	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	2	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Proteinuria	1/3 (33.3%)	3	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Renal and urinary disorders - Other, dysuria	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	1/6 (16.7%)	1
Renal and urinary disorders - Other, glucosuria	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	3	0/6 (0%)	0
Urinary retention	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	1/6 (16.7%)	1
Urine discoloration	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	1/6 (16.7%)	1
Reproductive system and breast disorders
Irregular menstruation	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Pelvic pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Cough	2/3 (66.7%)	2	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	1/3 (33.3%)	1	5/25 (20%)	6	1/6 (16.7%)	1
Dyspnea	2/3 (66.7%)	2	0/3 (0%)	0	3/6 (50%)	4	5/7 (71.4%)	6	0/3 (0%)	0	8/25 (32%)	10	2/6 (33.3%)	3
Epistaxis	1/3 (33.3%)	1	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	2	1/6 (16.7%)	1
Hiccups	1/3 (33.3%)	1	1/3 (33.3%)	1	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	3/25 (12%)	3	0/6 (0%)	0
Hoarseness	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Hypoxia	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Nasal congestion	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/7 (14.3%)	1	1/3 (33.3%)	1	0/25 (0%)	0	0/6 (0%)	0
Pleural effusion	0/3 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	2	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	2	1/6 (16.7%)	1
Pneumothorax	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Postnasal drip	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	2	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Productive cough	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	2/7 (28.6%)	3	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders - Other, Oropharyngeal pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders - Other, Rhinorrhea	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Sinus pain	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Sore throat	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Wheezing	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	2/25 (8%)	3	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/3 (33.3%)	1	2/3 (66.7%)	2	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	3/25 (12%)	3	0/6 (0%)	0
Nail discoloration	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	2	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Papulopustular rash	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Rash acneiform	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Rash maculo-papular	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	2/6 (33.3%)	2
Skin and subcutaneous tissue disorders - Other, Hidradenitis	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Skin and subcutaneous tissue disorders - Other, chest redness	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Skin and subcutaneous tissue disorders - Other, nail change	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	1/25 (4%)	1	0/6 (0%)	0
Skin hyperpigmentation	1/3 (33.3%)	2	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Skin hypopigmentation	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Skin ulceration	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Vascular disorders
Flushing	1/3 (33.3%)	1	0/3 (0%)	0	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	3/25 (12%)	4	2/6 (33.3%)	2
Hot flashes	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	1/7 (14.3%)	1	0/3 (0%)	0	0/25 (0%)	0	1/6 (16.7%)	1
Hypertension	3/3 (100%)	6	2/3 (66.7%)	4	4/6 (66.7%)	27	2/7 (28.6%)	7	0/3 (0%)	0	13/25 (52%)	54	2/6 (33.3%)	3
Hypotension	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/7 (0%)	0	1/3 (33.3%)	1	1/25 (4%)	1	0/6 (0%)	0
Lymphedema	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/7 (0%)	0	0/3 (0%)	0	0/25 (0%)	0	0/6 (0%)	0
Thromboembolic event	0/3 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	2	1/7 (14.3%)	1	0/3 (0%)	0	2/25 (8%)	2	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.