NeoplasmsPhase 1NCT02723864

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

A Phase 1 study testing Veliparib + VX-970 + Cisplatin in people with Neoplasms, run by National Cancer Institute (NCI) at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Neoplasms
What is being tested?: Veliparib + VX-970 + Cisplatin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 53 participants
Where: 3 sitesUnited States
Study dates: 9 Aug 2017to 31 Dec 2021
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 22Show fewer

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

Who cannot join

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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
MD Anderson Cancer Center
Houston, Texas, 77030-4096

Other trials in United States

About this study

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

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.

Read the 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

Conditions: Neoplasms
Being tested: Veliparib + VX-970 + Cisplatin
Keywords: Pharmacodynamic, DNA Damage Repair, BRCA Null, Apoptosis, Combination Therapy
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Veliparib + VX-970 + CisplatinDrug
Also called ABT-888 + M6620 (berzosertib) + Cisplatinum
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.

Study groups in NCT02723864
Study group	Role	What they receive
M6620 (VX-970)	Experimental	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 Receives: Drug: Veliparib + VX-970 + Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (2)

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
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).
Measured: Cycle 1 Day 1, and Cycle 1 Day 9 (i.e., one cycle = 21 days)
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
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.
Measured: 4 cycles (i.e., one cycle = 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Aug 201731 Dec 2021

First posted31 Mar 2016 (estimated)
Study start9 Aug 2017
Primary completion15 Dec 2020
Study completion31 Dec 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for NeoplasmsStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 53 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02723864
Sponsor's protocol ID: 160087
Other IDs: 16-C-0087
Status last verified: Jan 2022
First submitted: 30 Mar 2016
Last updated: 8 Feb 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: We will share IPD (clinical data) during the study and indefinitely via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

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. doi: 10.2174/1566524013666131111125515.
PubMed 24206132
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.
PubMed 23548269
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. doi: 10.1158/1078-0432.CCR-06-3039.
PubMed 17473206
O'Sullivan Coyne G, Do KT, Kummar S, Piha-Paul S, Rubinstein L, Kinders R, Parchment RE, Wilsker D, Ferry-Galow K, Miller B, Takebe N, Juwara L, Ong MJ, Bruns A, Hogu M, Naqash AR, Mittra A, Voth AR, Doroshow JH, Chen AP. Safety and Tolerability of Berzosertib, an Ataxia-Telangiectasia-Related Inhibitor, and Veliparib, an Oral Poly (ADP-ribose) Polymerase Inhibitor, in Combination With Cisplatin in Patients With Refractory Solid Tumors. JCO Precis Oncol. 2025 Jul;9:e2500055. doi: 10.1200/PO-25-00055. Epub 2025 Jul 16.
PubMed 40669022
Smith G, Alholm Z, Coleman RL, Monk BJ. DNA Damage Repair Inhibitors-Combination Therapies. Cancer J. 2021 Nov-Dec 01;27(6):501-505. doi: 10.1097/PPO.0000000000000561.
PubMed 34904813

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02723864
Acronym / sponsor ID: 160087
Conditions: Neoplasms
Keywords: Pharmacodynamic, DNA Damage Repair, BRCA Null, Apoptosis, Combination Therapy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 53 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 9 Aug 2017 (actual)
Primary completion: 15 Dec 2020 (actual)
Study completion: 31 Dec 2021 (actual)
First posted: 31 Mar 2016 (estimated)
Results: Posted 10 Jan 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

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.

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:

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

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
M6620 (VX-970)	Experimental	Drug: Veliparib + VX-970 + CisplatinM6620 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

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.

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Veliparib + VX-970 + CisplatinAlso: ABT-888 + M6620 (berzosertib) + CisplatinumAtaxia-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.	Drug	M6620 (VX-970)

Primary outcome

Number of Participants With Worst Grade 2 or Higher Adverse Events Occurring in >5% of Participants at Least Possibly Related to Study Drugs
Time frame: 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.

2 secondary outcomes

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
Time frame: Cycle 1 Day 1, and Cycle 1 Day 9 (i.e., one cycle = 21 days)
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
Time frame: 4 cycles (i.e., one cycle = 21 days)

Results and safety

Results posted to the registry on 10 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Level 1	3	2
Dose Level 2	3	2
Dose Level 3	6	5
Dose Level 4	7	7
Dose Level 5	3	2
Dose Level 6	25	14
Dose Level 7	6	4

Primary outcome: Number of Participants With Worst Grade 2 or Higher Adverse Events Occurring in >5% of Participants at Least Possibly Related to Study Drugs

Time frame: Cycle 1 (i.e., one cycle = 21 days). Count of participants. Unit: Participants

Measure	Grade 2 Adverse Events - Dose Level 1 n = 3	Grade 3 Adverse Events - Dose Level 1 n = 3	Grade 2 Adverse Events - Dose Level 2 n = 3	Grade 2 Adverse Events - Dose Level 3 n = 6	Grade 3 Adverse Events - Dose Level 3 n = 6	Grade 4 Adverse Events - Dose Level 3 n = 6	Grade 2 Adverse Events - Dose Level 4 n = 7	Grade 3 Adverse Events - Dose Level 4 n = 7	Grade 4 Adverse Events - Dose Level 4 n = 7	Grade 2 Adverse Events - Dose Level 5 n = 3	Grade 3 Adverse Events - Dose Level 5 n = 3	Grade 4 Adverse Events - Dose Level 5 n = 3	Grade 2 Adverse Events - Dose Level 6 n = 25	Grade 3 Adverse Events - Dose Level 6 n = 25	Grade 4 Adverse Events - Dose Level 6 n = 25	Grade 2 Adverse Events - Dose Level 7 n = 6	Grade 3 Adverse Events - Dose Level 7 n = 6	Grade 4 Adverse Events - Dose Level 7 n = 6
Alkaline phosphatase increased	1	0	0	1	0	0	0	1	0	1	0	0	0	0	0	0	0	0
Anemia	1	1	0	3	3	0	3	3	0	0	3	0	6	10	1	1	2	0
Creatinine increased	0	0	0	0	0	0	1	0	0	0	0	0	3	0	0	0	0	0
Fatigue	2	0	2	2	0	0	1	0	0	2	0	0	3	0	0	1	0	0
Hypertension	2	0	0	3	1	0	1	0	0	0	0	0	4	5	0	1	1	0
Hypomagnesemia	0	0	0	0	0	0	1	0	0	0	0	0	2	1	0	0	0	0
Hyponatremia	0	1	0	0	1	0	0	0	0	0	1	0	0	1	0	0	0	0
Hypophosphatemia	1	1	2

2 secondary outcomes are reported in the full results.

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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dose Level 1	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Dose Level 2	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Dose Level 3	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6
Dose Level 4	2 of 7 (28.6%)	7 of 7 (100%)	0 of 7
Dose Level 5	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Dose Level 6	14 of 25 (56%)	25 of 25 (100%)	1 of 25
Dose Level 7	0 of 6 (0%)	6 of 6 (100%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24206132Chen 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. doi: 10.2174/1566524013666131111125515.
Background: PubMed 23548269Huntoon 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.
Background: PubMed 17473206Donawho 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. doi: 10.1158/1078-0432.CCR-06-3039.
Derived from this study: PubMed 40669022O'Sullivan Coyne G, Do KT, Kummar S, Piha-Paul S, Rubinstein L, Kinders R, Parchment RE, Wilsker D, Ferry-Galow K, Miller B, Takebe N, Juwara L, Ong MJ, Bruns A, Hogu M, Naqash AR, Mittra A, Voth AR, Doroshow JH, Chen AP. Safety and Tolerability of Berzosertib, an Ataxia-Telangiectasia-Related Inhibitor, and Veliparib, an Oral Poly (ADP-ribose) Polymerase Inhibitor, in Combination With Cisplatin in Patients With Refractory Solid Tumors. JCO Precis Oncol. 2025 Jul;9:e2500055. doi: 10.1200/PO-25-00055. Epub 2025 Jul 16.
Derived from this study: PubMed 34904813Smith G, Alholm Z, Coleman RL, Monk BJ. DNA Damage Repair Inhibitors-Combination Therapies. Cancer J. 2021 Nov-Dec 01;27(6):501-505. doi: 10.1097/PPO.0000000000000561.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Individual participant dataSharing planned: Yes. We will share IPD (clinical data) during the study and indefinitely via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Alice P Chen, M.D. principal investigator

National Cancer Institute (NCI)

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Veliparib + VX-970 + Cisplatin in people with Neoplasms, run by National Cancer Institute (NCI) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Worst Grade 2 or Higher Adverse Events Occurring in >5% of Participants at Least Possibly Related to Study Drugs (time frame: Cycle 1 (i.e., one cycle = 21 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02723864, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2022.