Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Topotecan

Poly(ADP-ribose) Polymerase Inhibitors

Veliparib

Topoisomerase I Inhibitors

Enzyme Inhibitors

ABT-888

Background:

* PARP is an enzyme that is involved in the repair of damage to DNA. Levels of the enzyme are higher in tumor cells than in normal cells, and may play a part in resistance to cancer chemotherapy and radiation therapy. ABT-888 is an experimental drug that inhibits PARP and may help to increase the effectiveness of cancer treatments designed to damage DNA in cancer cells.
* Topotecan is a drug approved by the Food and Drug Administration for treating certain cancers.
* This dose escalation study will test the two drugs at successively higher doses in small groups of patients until the highest safe dose is determined.

Objectives:

* To test the safety of the combination of ABT-888 and Topotecan (TPT) and determine the highest dose of each drug that can be safely given to humans. This is the maximum tolerated dose (MTD).
* To learn how the combination of ABT-888 and TPT works in humans and how the body handles the drugs.
* To determine the side effects of the combination of ABT-888 and TPT at the tested doses.

Eligibility:

-Patients with solid tumors, lymphomas and chronic lymphocytic leukemia whose disease has progressed following standard therapy or for whom standard treatments are not available.

Design:

* ABT-888 and TPT are given in 21-day treatment cycles. At the start of the study, TPT is infused through a vein over 30 minutes about a week before cycle 1 starts. Starting on day 1 of cycle 1, ABT-888 is given by mouth twice a day for 7 days. TPT is given through a vein daily for 4 days starting on day 2. After the last dose of ABT-888 day 7, no more treatment is given for the rest of the 21-day cycle.
* For the remaining cycles, ABT-888 is given twice a day by mouth on days 1 to 7 of each cycle, and TPT is given through a vein daily on days 1 to 5 of each cycle.
* The first three to six patients enrolled in the study take the smallest study dose of the drugs. If they do not develop significant adverse side effects, successive small groups of patients take the drug at increasingly higher doses until the MTD is reached. Additional patients enrolled receive the MTD.
* Patients have periodic clinic visits for their TPT infusions and for tests and examinations. Evaluations include measurement of vital signs, physical examinations, blood and urine tests, electrocardiograms and CT or other imaging tests, such as ultrasound or MRI. Tumor biopsies may be requested to study the effects of the drugs on the...

Background:

* The PARP family of enzymes is characterized by the ability to poly (ADP-ribosyl)ate protein substrates. PARP-1 and PARP-2 play a critical role in the maintenance of genomic stability by regulating a variety of DNA repair mechanisms.
* Poly (ADP-ribosylated) PARP-1 has been shown to block the formation of topo 1-DNA cleavage and accelerate the removal of camptothecin-stabilized topo 1-DNA complexes. PARP-1 inhibition may therefore prevent efficient repair of DNA damage induced by topoisomerase 1 inhibitors. ABT-888 is an oral PARP inhibitor and topotecan is a topoisomerase I inhibitor.

Objectives:

* Establish the safety and tolerability of the combination of ABT-888 with topotecan hydrochloride in patients with refractory solid tumors and lymphomas.
* Establish the maximum tolerated dose of the combination of ABT-888 with topotecan hydrochloride.
* Evaluate the pharmacokinetics of each agent alone and in combination.
* Determine the effects of the study treatment on the level of PARP inhibition and DNA damage in PBMCs and tumor samples.

Eligibility:

* Patients with histologically documented solid tumors and lymphoid malignancies (lymphoma and CLL) whose disease has progressed following standard therapy or who have no acceptable standard treatment options.
* No major surgery, radiation or chemotherapy within four weeks prior to study enrollment, and recovered from toxicities of prior therapies to at least eligibility levels.

Study Design:

* Cycle 1, dose levels -1 to 7 and 1B: Topotecan (TPT) will be administered intravenously over 30 minutes as a single dose on days 1-5. Starting on day 2, ABT-888 will be administered orally twice a day on a q12 hour schedule for 4 days (D2-5). Following the completion of study drug administration on day 5, no further treatment will be administered for the rest of this 21-day cycle. Growth factors will be administered prophylactically starting Cycle 1 to patients on dose level 1B only.
* Cycle 2 and beyond, dose levels -1 to 7 and 1B: ABT-888 will be administered twice a day on a q12 hour schedule orally on days 1-5. TPT will be given IV daily from days 1-5, in a 21-day cycle. Growth factors will be administered prophylactically to patients on dose level 1B only.
* All cycles, dose levels -2 and 1A to 5A: ABT-888 will be administered on day 1 only for dose levels -2 and 1A, 2A, 3A, and 4A. For dose level 5A, ABT-888 will be administered on days 1 and 2 of each cycle. TPT will be given IV daily from days 1-5, in a 21-day cycle.
* Dose escalation will proceed as outlined below. Once maximum tolerated dose (MTD) is established, 6 additional patients will be enrolled at the MTD to further define the dose and evaluate PD studies at this dose level.

Safety Study of ABT-888 Plus Topotecan Hydrochloride to Treat Patients With Solid Tumors and Lymphomas

A Phase I Study of ABT-888 in Combination With Topotecan Hydrochloride in Adults With Refractory Solid Tumors and Lymphomas

National Cancer Institute (NCI)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Hormones

Talazoparib

talazoparib plus enzalutamide

Placebo plus enzalutamide

Pfizer CT.gov Call Center

The purpose of the study is to evaluate the safety and efficacy of talazoparib in combination with enzalutamide compared with placebo in combination with enzalutamide in participants with DDR-deficient mCSPC.

The study will have 5 periods: prescreening, screening, double-blind treatment, safety follow-up, and long-term follow-up.

Approximately 550 men with mCSPC will be randomized. Eligible participants will be randomly assigned to either of 2 treatment groups as follows:

* Talazoparib in combination with enzalutamide.
* Placebo capsules identical in appearance to talazoparib capsules in combination with enzalutamide.

Talazoparib or identical placebo treatment will be blinded. Enzalutamide (160 mg/day) will be open label. The dose of talazoparib/placebo to be given in combination with enzalutamide is 0.5 mg once daily. Participants with moderate renal impairment (eGFR 30-59 mL/min/1.73 m2 by the MDRD equation) at screening may be enrolled and the talazoparib/placebo dose will be 0.35 mg once daily.

Parallel: Participants are assigned to one of two or more groups in parallel for the duration of the study

Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC

TALAPRO-3: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, STUDY OF TALAZOPARIB WITH ENZALUTAMIDE VERSUS PLACEBO WITH ENZALUTAMIDE IN MEN WITH DDR GENE MUTATED METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

time from the date of randomization to first objective evidence of radiographic progression or death, whichever occurs first

time from randomization to death from any cause

proportion of patients with measurable soft tissue disease at baseline with objective response per RECIST 1.1

duration of responses in patients with measurable soft tissue disease at baseline per RECIST 1.1

proportion of patients with PSA response grater than or equal to 50%

Time from randomization to initiation of antineoplastic therapy

time from randomization to first symptomatic skeletal event (symptomatic fractures, spinal cord compression, surgery or radiation to the bone whichever is first)

time from randomization to opiate use for prostate cancer pain

AEs and SAEs incidence by type and severity (graded by NCI CTCAE version 4.03)

plasma concentrations of enzalutamide and its metabolite

change from baseline in patient-reported pain symptoms per Brief Pain Inventory Short Form (BPI-SF)

time to deterioration in patient-reported pain symptoms per Brief Pain Inventory Short Form (BPI-SF)

change from baseline in participant-reported general health status per EQ-5D-5L

change from baseline in patient-reported Global health status/QoL per EORTC QLQ-C30

time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30

time to definitive deterioration in disease specific urinary symptoms per EORTC QLQ-PR25

Astellas Pharma Inc

Pfizer

Alkylating Agents

Phase 1 Single Arm Multicenter Study to Assess the Safety and Tolerability of LP-184 in Patients with Advanced Solid Tumors

LP-184 is a small molecule alkylating agent causing tumor cell death through DNA damage.

LP-184

Lyza Trejo

Amie Winn

Joseph T Beck

Trong Nguyen

Stefi Guillen

Vu Phan, MD

Nihal Abdulla, MD

Nowsheen Azeemuddin

Bruce Bank, MD

Marina Messinger, MD

Gary E Kay, MD

Ronald J Shade, MD

Tonia Cabai, NP-C

Cristyn Savoia, APN

Christina Raynor

Cassandra Brass

Misty Shields

Michael Buchanan

John Hamm

Ikenna Opurum

Anthony Olszanski, MD

Jasmine Deblanc

Casey Larsen

William McKean, MD

Reggie Ewesuedo, MD

The primary objective of this study is to evaluate the safety, tolerability, MTD and RP2D of LP-184 in patients with advanced solid tumors who have relapsed from or are refractory to standard therapy or for whom no standard therapy is available. The secondary objectives are to characterize the PK of LP-184 and its metabolites in plasma and assess clinical activity of LP-184.

Patients who meet all eligibility criteria will be enrolled to receive treatment with LP-184 at a dose determined based on the available cohort at the time of each patient's enrollment. Patients will receive LP-184 infusion during Day 1 and Day 8 of each 21-day cycle, for a minimum of two cycles. Patients will be monitored for safety, PK, and clinical activity. Dose escalation is planned with minimum of 3 patient cohorts (starting at dose level 1). After selection of the maximum tolerated dose (MTD), additional patients will be enrolled at two dose levels, including the MTD, as determined by the Safety Review Committee, until at least 10 patients each are treated at each dose to determine the recommended phase 2 dose.

Study of LP-184 in Patients With Advanced Solid Tumors

A Phase 1A Dose Escalation Study of LP-184 in Patients With Advanced or Metastatic Solid Tumors.

Incidence and severity of AEs graded according to the NCI CTCAE, version 5.0, clinical laboratory and ECG abnormalities defined as DLTs

To determine the Cmax from plasma concentration in patients

To determine the Tmax from plasma concentration in patients

To determine the half-life of LP-184 in patients

Area under the Plasma Concentration versus Time Curve (AUC) of LP-184 and major metabolite from time zero to 24 hours post infusion (AUC 0 to 24)

Lantern Pharma Inc.

Symptoms and General Pathology

Gland and Hormone Related Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Prexasertib

Protein Kinase Inhibitors

Participants received 105 milligram per square meter (mg/m²) prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.

Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy.

Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor.

Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The purpose of this study is to evaluate the efficacy and safety of prexasertib in women with platinum-resistant or refractory recurrent ovarian cancer.

A Study of Prexasertib (LY2606368) in Platinum-Resistant or Refractory Recurrent Ovarian Cancer

A Phase 2 Study of Prexasertib in Platinum-Resistant or Refractory Recurrent Ovarian Cancer

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100.

Pharmacokinetics(PK): Maximum Plasma Concentration of Prexasertib. The same dose was administered to Cohort 1, 2, 3 and 4 and were combined for analysis.

DCR is defined as the number of participants who achieve a best overall response of CR, PR or SD for ≥4 months as determined by per RECIST version 1.1. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion; SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Disease control rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100.

Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.

CA-125 response is defined as ≥50% reduction in CA-125 levels from a pretreatment sample. The response must be confirmed and maintained for ≥28 days according to GCIG criteria. Participants must have a pretreatment sample that is ≥2 times the upper limit of the reference range and obtained within 2 weeks before starting the treatment.

Progression-Free Survival (PFS) is defined as the time from the date of enrollment until the first occurrence of documented disease progression per RECIST 1.1, or death from any cause in the absence of progressive disease (PD). Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.

Overall survival (OS) is defined as the time from the date of enrollment until death from any cause. If the participant is alive, lost to follow-up or withdrawn from study at the time of data analysis, OS data will be censored on the last date the participant is known to be alive.

Eli Lilly and Company

All randomized participants who received at least one dose.

Prexasertib Cohort 1

Prexasertib Cohort 2

Prexasertib Cohort 3

Prexasertib Cohort 4

Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

South Korea

Belgium

United States

United Kingdom

Italy

Israel

Australia

Spain

Region of Enrollment

All randomized participants who received at least one dose of study drug.

Chief Medical Officer

Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR)

Cycle 1

Cycle 2

Cycle 4

Cycle 6

Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. (Participants combined from all the Cohorts 1 to 4)

All randomized participants who received at least one dose of study drug and had evaluable PK data. Cohort 1, 2, 3 and 4 received the same dose and were combined per protocol.

Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Prexasertib

Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) for at Least 4 Months

All randomized participants who received at least one dose of study drug and had CR or PR responses. Number of participants censored Cohort 1 = 0, Cohort 2 = 1, Cohort 3 = 0 and Cohort 4 = 0.

Duration of Response

Percentage of Participants With at Least a 50% Reduction in CA-125 Levels From Baseline

All randomized participants who received at least one dose of study drug. Number of participants censored Cohort 1 = 6, Cohort 2 = 4, Cohort 3 = 4 and Cohort 4 = 4.

Progression-Free Survival

All randomized participants who received at least one dose of study drug and had overall survival data. Number of participants censored Cohort 1 = 18, Cohort 2 = 12, Cohort 3 = 12 and Cohort 4 = 4.

Overall Survival

Overall Study

Cisplatin

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

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.

Veliparib + VX-970 + Cisplatin

Alice P Chen, M.D.

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.

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

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

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

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).

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.

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.

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).

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.

Principal Investigator

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)

Dose Level 1

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)

Dose Level 2

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)

Dose Level 3

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)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety Study of ABT-888 Plus Topotecan Hydrochloride to Treat Patients With Solid Tumors and Lymphomas	NCT00553189	Solid Tumors Lymphomas	ABT-888 Topotecan	18 Years -	National Institutes of Health Clinical Center (CC)
Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC	NCT04821622	Prostate Cancer	talazoparib plu... Placebo plus en...	18 Years -	Pfizer
Study of LP-184 in Patients With Advanced Solid Tumors	NCT05933265	Advanced Solid ...	LP-184	18 Years -	Lantern Pharma Inc.
Safety Study of ABT-888 Plus Topotecan Hydrochloride to Treat Patients With Solid Tumors and Lymphomas	NCT00553189	Solid Tumors Lymphomas	ABT-888 Topotecan	18 Years -	National Institutes of Health Clinical Center (CC)
A Study of Prexasertib (LY2606368) in Platinum-Resistant or Refractory Recurrent Ovarian Cancer	NCT03414047	Ovarian Cancer	Prexasertib	18 Years -	Eli Lilly and Company
Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin in People With Refractory Solid Tumors	NCT02723864	Neoplasms	Veliparib + VX-...	18 Years -	National Institutes of Health Clinical Center (CC)
Predictive Biomarkers for Response to Nivolumab in Head and Neck Squamous Cell Carcinoma	NCT03652142	HNSCC DNA Damage DNA Double Stra...	Biomarker Resea... Nivolumab	18 Years -	Attikon Hospital
Phase II ABT-888 With Cyclophosphamide	NCT01306032	Ovarian Cancer Primary Periton... Serous Carcinom... Triple-Negative... Fallopian Tube ...	ABT-888 Cyclophosphamid...	18 Years -	National Institutes of Health Clinical Center (CC)
Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC	NCT04821622	Prostate Cancer	talazoparib plu... Placebo plus en...	18 Years -	Pfizer

Spots Global Cancer Trial Database for dna damage repair