Skip to main content
Springer Nature Link
Log in

A phase 1 study of veliparib (ABT-888) plus weekly carboplatin and paclitaxel in advanced solid malignancies, with an expansion cohort in triple negative breast cancer (TNBC) (ETCTN 8620)

  • Clinical trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

See More

Veliparib is a poly-ADP-ribose polymerase (PARP) inhibitor, and it has clinical activity with every 3 weeks carboplatin and paclitaxel. In breast cancer, weekly paclitaxel is associated with improved overall survival. We aimed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib with weekly carboplatin and paclitaxel as well as safety, pharmacokinetics, and preliminary clinical activity in triple negative breast cancer (TNBC).

Methods

Patients with locally advanced/metastatic solid tumors and adequate organ function were eligible. A standard 3 + 3 dose-escalation design was followed by a TNBC expansion cohort. Veliparib doses ranging from 50 to 200 mg orally bid were tested with carboplatin (AUC 2) and paclitaxel (80 mg/m2) given weekly in a 21-day cycle. Adverse events (AE) were evaluated by CTCAE v4.0, and objective response rate (ORR) was determined by RECIST 1.1.

Results

Thirty patients were enrolled, of whom 22 had TNBC. Two dose-limiting toxicities were observed. The RP2D was determined to be 150 mg PO bid veliparib with weekly carboplatin and paclitaxel 2 weeks on, 1 week off, based on hematologic toxicity requiring dose reduction in the first 5 cycles of treatment. The most common grade 3/4 AEs included neutropenia, anemia, and thrombocytopenia. PK parameters of veliparib were comparable to single-agent veliparib. In 23 patients with evaluable disease, the ORR was 65%. In 19 patients with TNBC with evaluable disease, the ORR was 63%.

Conclusion

Veliparib can be safely combined with weekly paclitaxel and carboplatin, and this triplet combination has promising clinical activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

Data availability

Further data are available upon reasonable request after permission of the sponsor.

References

  1. Sorlie T, Wang Y, Xiao C, Johnsen H, Naume B, Samaha RR, Borresen-Dale AL (2006) Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms. BMC Genomics 7:127

    Article  PubMed  PubMed Central  Google Scholar 

  2. Foulkes WD, Brunet JS, Stefansson IM, Straume O, Chappuis PO, Begin LR, Hamel N, Goffin JR, Wong N, Trudel M et al (2004) The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer. Can Res 64(3):830–835

    Article  CAS  Google Scholar 

  3. Lakhani SR, Van De Vijver MJ, Jacquemier J, Anderson TJ, Osin PP, McGuffog L, Easton DF (2002) The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 20(9):2310–2318

    Article  CAS  PubMed  Google Scholar 

  4. Isakoff SJ, Mayer EL, He L, Traina TA, Carey LA, Krag KJ, Rugo HS, Liu MC, Stearns V, Come SE et al (2015) TBCRC009: a multicenter phase II clinical trial of platinum monotherapy with biomarker assessment in metastatic triple-negative breast cancer. J Clin Oncol 33(17):1902–1909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Vos S, van Diest PJ, Moelans CB (2018) A systematic review on the frequency of BRCA promoter methylation in breast and ovarian carcinomas of BRCA germline mutation carriers: mutually exclusive, or not? Crit Rev Oncol Hematol 127:29–41

    Article  PubMed  Google Scholar 

  6. Zhang L, Long X (2015) Association of BRCA1 promoter methylation with sporadic breast cancers: evidence from 40 studies. Sci Rep 5:17869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Turner N, Tutt A, Ashworth A (2004) Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer 4(10):814–819

    Article  CAS  PubMed  Google Scholar 

  8. Turner NC, Reis-Filho JS (2006) Basal-like breast cancer and the BRCA1 phenotype. Oncogene 25(43):5846–5853

    Article  CAS  PubMed  Google Scholar 

  9. Schouten PC, Linn SC (2015) Challenges in the use of DNA Repair deficiency as a biomarker in breast cancer. J Clin Oncol 33(17):1867–1869

    Article  PubMed  Google Scholar 

  10. Kondrashova O, Topp M, Nesic K, Lieschke E, Ho GY, Harrell MI, Zapparoli GV, Hadley A, Holian R, Boehm E et al (2018) Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma. Nat Commun 9(1):3970

    Article  PubMed  PubMed Central  Google Scholar 

  11. Tomoda T, Kurashige T, Moriki T, Yamamoto H, Fujimoto S, Taniguchi T (1991) Enhanced expression of poly(ADP-ribose) synthetase gene in malignant lymphoma. Am J Hematol 37(4):223–227

    Article  CAS  PubMed  Google Scholar 

  12. Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P et al (2018) Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med 24(5):628–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ossovskaya V, Koo IC, Kaldjian EP, Alvares C, Sherman BM (2010) Upregulation of poly (ADP-Ribose) polymerase-1 (PARP1) in Triple-negative breast cancer and other primary human tumor types. Genes Cancer 1(8):812–821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shiobara M, Miyazaki M, Ito H, Togawa A, Nakajima N, Nomura F, Morinaga N, Noda M (2001) Enhanced polyadenosine diphosphate-ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma. J Gastroenterol Hepatol 16(3):338–344

    Article  CAS  PubMed  Google Scholar 

  15. Litton JK, Rugo HS, Ettl J, Hurvitz SA, Goncalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M et al (2018) Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med 379(8):753–763

    Article  CAS  PubMed  Google Scholar 

  16. Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A et al (2017) Olaparib for Metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 377(6):523–533

    Article  CAS  PubMed  Google Scholar 

  17. Nishikawa T, Matsumoto K, Tamura K, Yoshida H, Imai Y, Miyasaka A, Onoe T, Yamaguchi S, Shimizu C, Yonemori K et al (2017) Phase 1 dose-escalation study of single-agent veliparib in Japanese patients with advanced solid tumors. Cancer Sci 108(9):1834–1842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Steffensen KD, Adimi P, Jakobsen A (2017) Veliparib monotherapy to patients with BRCA germ line mutation and platinum-resistant or partially platinum-sensitive relapse of epithelial ovarian cancer: a phase I/II study. Int J gynecol cancer 27(9):1842–1849

    Article  PubMed  Google Scholar 

  19. Anampa J, Chen A, Wright J, Patel M, Pellegrino C, Fehn K, Sparano JA, Andreopoulou E (2018) Phase I trial of veliparib, a Poly ADP ribose polymerase inhibitor, plus metronomic cyclophosphamide in metastatic HER2-negative breast cancer. Clin Breast Cancer 18(1):e135–e142

    Article  CAS  PubMed  Google Scholar 

  20. Gray HJ, Bell-McGuinn K, Fleming GF, Cristea M, Xiong H, Sullivan D, Luo Y, McKee MD, Munasinghe W, Martin LP (2018) Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies. Gynecol Oncol 148(3):507–514

    Article  CAS  PubMed  Google Scholar 

  21. Isakoff SJ, Puhalla S, Domchek SM, Friedlander M, Kaufman B, Robson M, Telli ML, Dieras V, Han HS, Garber JE et al (2017) A randomized phase II study of veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in BRCA1/2 metastatic breast cancer: design and rationale. Future Oncol 13(4):307–320

    Article  CAS  PubMed  Google Scholar 

  22. Nishio S, Takekuma M, Takeuchi S, Kawano K, Tsuda N, Tasaki K, Takahashi N, Abe M, Tanaka A, Nagasawa T et al (2017) Phase 1 study of veliparib with carboplatin and weekly paclitaxel in Japanese patients with newly diagnosed ovarian cancer. Cancer Sci 108(11):2213–2220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rugo HS, Olopade OI, DeMichele A, Yau C, van’t Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J et al (2016) Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Medicine 375(1):23–34

    Article  CAS  Google Scholar 

  24. Somlo G, Frankel PH, Arun BK, Ma CX, Garcia AA, Cigler T, Cream LV, Harvey HA, Sparano JA, Nanda R et al (2017) Efficacy of the PARP Inhibitor veliparib with carboplatin or as a single agent in patients with germline BRCA1- or BRCA2-associated metastatic breast cancer: california cancer consortium trial NCT01149083. Clin Cancer Res 23(15):4066–4076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Stoller R, Schmitz JC, Ding F, Puhalla S, Belani CP, Appleman L, Lin Y, Jiang Y, Almokadem S, Petro D et al (2017) Phase I study of veliparib in combination with gemcitabine. Cancer Chemother Pharmacol 80(3):631–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Appleman LJ, Beumer JH, Jiang Y, Lin Y, Ding F, Puhalla S, Swartz L, Owonikoko TK, Donald Harvey R, Stoller R et al (2019) Phase 1 study of veliparib (ABT-888), a poly (ADP-ribose) polymerase inhibitor, with carboplatin and paclitaxel in advanced solid malignancies. Cancer Chemother Pharmacol 84(6):1289–1301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pothuri B, Brodsky AL, Sparano JA, Blank SV, Kim M, Hershman DL, Tiersten A, Kiesel BF, Beumer JH, Liebes L et al (2020) Phase I and pharmacokinetic study of veliparib, a PARP inhibitor, and pegylated liposomal doxorubicin (PLD) in recurrent gynecologic cancer and triple negative breast cancer with long-term follow-up. Cancer Chemother Pharmacol 85(4):741–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Manzo J, Puhalla S, Pahuja S, Ding F, Lin Y, Appleman L, Tawbi H, Stoller R, Lee JJ, Diergaarde B et al (2022) A phase 1 and pharmacodynamic study of chronically-dosed, single-agent veliparib (ABT-888) in patients with BRCA1- or BRCA2-mutated cancer or platinum-refractory ovarian or triple-negative breast cancer. Cancer Chemother Pharmacol 89(5):721–735

    Article  CAS  PubMed  Google Scholar 

  29. Chen Q, Kassab MA, Dantzer F, Yu X (2018) PARP2 mediates branched poly ADP-ribosylation in response to DNA damage. Nat Commun 9(1):3233

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zhu G, Chang P, Lippard SJ (2010) Recognition of platinum-DNA damage by poly(ADP-ribose) polymerase-1. Biochemistry 49(29):6177–6183

    Article  CAS  PubMed  Google Scholar 

  31. Helleday T (2011) The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Mol Oncol 5(4):387–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dhawan MS, Bartelink IH, Aggarwal RR, Leng J, Zhang JZ, Pawlowska N, Terranova-Barberio M, Grabowsky JA, Gewitz A, Chien AJ et al (2017) Differential toxicity in patients with and without DNA repair mutations: phase I Study of carboplatin and talazoparib in advanced solid tumors. Clin Cancer Res 23(21):6400–6410

    Article  CAS  PubMed  Google Scholar 

  33. Hopkins TA, Ainsworth WB, Ellis PA, Donawho CK, DiGiammarino EL, Panchal SC, Abraham VC, Algire MA, Shi Y, Olson AM et al (2019) PARP1 trapping by PARP inhibitors drives cytotoxicity in both cancer cells and healthy bone marrow. Mol Cancer Res 17(2):409–419

    Article  CAS  PubMed  Google Scholar 

  34. Parise RA, Shawaqfeh M, Egorin MJ, Beumer JH (2008) Liquid chromatography-mass spectrometric assay for the quantitation in human plasma of ABT-888, an orally available, small molecule inhibitor of poly(ADP-ribose) polymerase. J Chromatogr B 872(1–2):141–147

    Article  CAS  Google Scholar 

  35. Colville H, Dzadony R, Kemp R, Stewart S, Zeh HJ 3rd, Bartlett DL, Holleran J, Schombert K, Kosovec JE, Egorin MJ et al (2010) In vitro circuit stability of 5-fluorouracil and oxaliplatin in support of hyperthermic isolated hepatic perfusion. J Extra Corpor Technol 42(1):75–79

    PubMed  PubMed Central  Google Scholar 

  36. Parise RA, Ramanathan RK, Zamboni WC, Egorin MJ (2003) Sensitive liquid chromatography-mass spectrometry assay for quantitation of docetaxel and paclitaxel in human plasma. J Chromatogr B 783(1):231–236

    Article  CAS  Google Scholar 

  37. Landrum LM, Brady WE, Armstrong DK, Moore KN, DiSilvestro PA, O’Malley DM, Tenney ME, Rose PG, Fracasso PM (2016) A phase I trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer: An NRG oncology/gynecologic oncology group study. Gynecol Oncol 140(2):204–209

    Article  CAS  PubMed  Google Scholar 

  38. Kelly K, Crowley J, Bunn PA Jr, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF et al (2001) Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non–small-cell lung cancer: a Southwest oncology group trial. J Clin Oncol 19(13):3210–3218

    Article  CAS  PubMed  Google Scholar 

  39. Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R et al (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a gynecologic oncology group study. J Clin Oncol 21(17):3194–3200

    Article  CAS  PubMed  Google Scholar 

  40. Coleman RL, Sill MW, Bell-McGuinn K, Aghajanian C, Gray HJ, Tewari KS, Rubin SC, Rutherford TJ, Chan JK, Chen A et al (2015) A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation—An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol 137(3):386–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Rodler E, Sharma P, Barlow WE, Gralow JR, Puhalla SL, Anders CK, Goldstein L, Tripathy D, Brown-Glaberman UA, Huynh T-T et al (2023) Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. https://doi.org/10.1016/S1470-2045(22)00739-2

    Article  PubMed  Google Scholar 

  42. Loibl S, O’Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M, von Minckwitz G, Maag D et al (2018) Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol 19(4):497–509

    Article  CAS  PubMed  Google Scholar 

  43. Dieras V, Han HS, Kaufman B, Wildiers H, Friedlander M, Ayoub JP, Puhalla SL, Bondarenko I, Campone M, Jakobsen EH et al (2020) Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 21(10):1269–1282

    Article  CAS  PubMed  Google Scholar 

  44. Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL et al (2019) Veliparib with First-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med 381(25):2403–2415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Balmana J, Tung NM, Isakoff SJ, Grana B, Ryan PD, Saura C, Lowe ES, Frewer P, Winer E, Baselga J et al (2014) Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors. Ann oncol 25(8):1656–1663

    Article  CAS  PubMed  Google Scholar 

  46. Dent RA, Lindeman GJ, Clemons M, Wildiers H, Chan A, McCarthy NJ, Singer CF, Lowe ES, Watkins CL, Carmichael J (2013) Phase I trial of the oral PARP inhibitor olaparib in combination with paclitaxel for first- or second-line treatment of patients with metastatic triple-negative breast cancer. Breast Cancer Res 15(5):R88

    Article  PubMed  PubMed Central  Google Scholar 

  47. Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, Colombo N, Spacek J, Vuylsteke P, Hirte H et al (2015) Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol 16(1):87–97

    Article  CAS  PubMed  Google Scholar 

  48. van der Noll R, Jager A, Ang JE, Marchetti S, Mergui-Roelvink MWJ, Lolkema MP, de Jonge MJA, van der Biessen DA, Brunetto AT, Arkenau HT et al (2020) Phase I study of continuous olaparib capsule dosing in combination with carboplatin and/or paclitaxel (Part 1). Invest New Drugs 38(4):1117–1128

    Article  PubMed  Google Scholar 

  49. Lee JM, Hays JL, Annunziata CM, Noonan AM, Minasian L, Zujewski JA, Yu M, Gordon N, Ji J, Sissung TM et al (2014) Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. JNCI 106(6):dju089

    Article  PubMed  PubMed Central  Google Scholar 

  50. Lampert EJ, Hays JL, Kohn EC, Annunziata CM, Minasian L, Yu M, Gordon N, Sissung TM, Chiou VL, Figg WD et al (2019) Phase I/Ib study of olaparib and carboplatin in heavily pretreated recurrent high-grade serous ovarian cancer at low genetic risk. Oncotarget 10(30):2855–2868

    Article  PubMed  PubMed Central  Google Scholar 

  51. Leal TA, Sharifi MN, Chan N, Wesolowski R, Turk AA, Bruce JY, O’Regan RM, Eickhoff J, Barroilhet LM, Malhotra J et al (2022) A phase I study of talazoparib (BMN 673) combined with carboplatin and paclitaxel in patients with advanced solid tumors (NCI9782). Cancer Med 11(21):3969–3981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Atrafi F, Groen HJM, Byers LA, Garralda E, Lolkema MP, Sangha RS, Viteri S, Chae YK, Camidge DR, Gabrail NY et al (2019) A phase I dose-escalation study of veliparib combined with carboplatin and etoposide in patients with extensive-stage small cell lung cancer and other solid tumors. Clin Cancer Res 25(2):496–505

    Article  CAS  PubMed  Google Scholar 

  53. Rodler ET, Kurland BF, Griffin M, Gralow JR, Porter P, Yeh RF, Gadi VK, Guenthoer J, Beumer JH, Korde L et al (2016) Phase I study of veliparib (ABT-888) combined with cisplatin and vinorelbine in advanced triple-negative breast cancer and/or BRCA mutation-associated breast cancer. Clin Cancer Res 22(12):2855–2864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ramalingam SS, Blais N, Mazieres J, Reck M, Jones CM, Juhasz E, Urban L, Orlov S, Barlesi F, Kio E et al (2017) Randomized, placebo-controlled, phase ii study of veliparib in combination with carboplatin and paclitaxel for advanced/metastatic non-small cell lung cancer. Clin Cancer Res 23(8):1937–1944

    Article  CAS  PubMed  Google Scholar 

  55. Han HS, Dieras V, Robson M, Palacova M, Marcom PK, Jager A, Bondarenko I, Citrin D, Campone M, Telli ML et al (2018) Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study. Ann oncol 29(1):154–161

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported in part by NCI (Grant Nos. U01CA099168, UM1CA186690, and U24CA247643). This project used the UPMC Hillman Cancer Center Cancer Pharmacokinetics and Pharmacodynamics Facility (CPPF) and was supported in part by award P30CA047904. The project described was supported by the National Institutes of Health through (Grant No. UL1TR001857). This work was also supported by a Conquer Cancer Foundation Career Development Award to Shannon Puhalla.

Author information

Author notes

  1. Jan H. Beumer

    Present address: UPMC Hillman Cancer Center, Hillman Research Pavilion, Room G27E, 5117 Centre Avenue, Pittsburgh, PA, 15213-1863, USA

  2. Shannon Puhalla

    Present address: UPMC Magee Women’s Hospital, 300 Halket Street, Pittsburgh, PA, 15213, USA

  3. Monica K. Malhotra and Shalu Pahuja Co-first author.

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Monica K. Malhotra, Shalu Pahuja, Leonard J. Appleman, Hussein A. Tawbi, Ronald G. Stoller, James J. Lee, Leisha A. Emens, Edward Chu, Jan H. Beumer & Shannon Puhalla

  2. Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA

    Brian F. Kiesel, Leonard J. Appleman, Hussein A. Tawbi, Ronald G. Stoller, James J. Lee, Edward Chu, Jan H. Beumer & Shannon Puhalla

  3. Department of Pharmaceutical Sciences, School of Pharmacy, Pittsburgh, PA, USA

    Brian F. Kiesel & Jan H. Beumer

  4. Biostatistics Facility, UPMC Hillman Cancer Center, Pittsburgh, PA, USA

    Fei Ding

  5. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Yan Lin

  6. UPMC Hillman Cancer Center, Pittsburgh, PA, USA

    Yan Lin

  7. Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA, USA

    Chandra P. Belani

  8. Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA

    S. Percy Ivy

  9. AbbVie Laboratories, North Chicago, IL, USA

    Vincent L. Giranda & Stacie Peacock Shepherd

  10. Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA

    Leisha A. Emens

  11. Cancer Therapeutics Program, Montefiore Einstein Cancer Center, Bronx, NY, USA

    Edward Chu

  12. Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, USA

    Alice P. Chen

  13. Center for Cancer Research, National Cancer Institute, Bethesda, USA

    Alice P. Chen

Authors
  1. Monica K. Malhotra
    View author publications

    Search author on:PubMed Google Scholar

  2. Shalu Pahuja
    View author publications

    Search author on:PubMed Google Scholar

  3. Brian F. Kiesel
    View author publications

    Search author on:PubMed Google Scholar

  4. Leonard J. Appleman
    View author publications

    Search author on:PubMed Google Scholar

  5. Fei Ding
    View author publications

    Search author on:PubMed Google Scholar

  6. Yan Lin
    View author publications

    Search author on:PubMed Google Scholar

  7. Hussein A. Tawbi
    View author publications

    Search author on:PubMed Google Scholar

  8. Ronald G. Stoller
    View author publications

    Search author on:PubMed Google Scholar

  9. James J. Lee
    View author publications

    Search author on:PubMed Google Scholar

  10. Chandra P. Belani
    View author publications

    Search author on:PubMed Google Scholar

  11. Alice P. Chen
    View author publications

    Search author on:PubMed Google Scholar

  12. Vincent L. Giranda
    View author publications

    Search author on:PubMed Google Scholar

  13. Stacie Peacock Shepherd
    View author publications

    Search author on:PubMed Google Scholar

  14. Leisha A. Emens
    View author publications

    Search author on:PubMed Google Scholar

  15. S. Percy Ivy
    View author publications

    Search author on:PubMed Google Scholar

  16. Edward Chu
    View author publications

    Search author on:PubMed Google Scholar

  17. Jan H. Beumer
    View author publications

    Search author on:PubMed Google Scholar

  18. Shannon Puhalla
    View author publications

    Search author on:PubMed Google Scholar

Corresponding authors

Correspondence to Jan H. Beumer or Shannon Puhalla.

Ethics declarations

Conflict of interest

Jan Beumer’s institute received research support from AbbVie. Leisha Emens has received research support from Aduro Biotech, AstraZeneca, Breast Cancer Research Foundation, Corvus, Department of Defense, EMD Serono, Genentech, HeritX, Inc., Maxcyte, Merck, National Cancer Institute, NSABP Foundation, Roche, Translational Breast Cancer Research Consortium, and has served as a consultant for AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Genentech, Gritstone, Lilly, Macrogenics, Medimmune, Molecuvax, Novartis, Peregrine, Replimune, Roche, Syndax, and Vaccinex. She has also received royalties from Aduro Biotech. Shannon Puhalla has received research support from AbbVie, Pfizer, Lilly, Novartis, Incyte, Covance-Bayer, AstraZeneca, Genentech, Medivation and has been a consultant for AbbVie, MedImmune, Celldex, Puma, Pfizer, AstraZeneca, Esai, and Nanostring. Stacie Shepherd is a former employee of Abbott, AbbVie, and Corcept and holds Abbott, AbbVie, and Corcept stocks.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Concent to participations

The authors would like to thank all of the participating patients and their families and the network of investigators, research nurses and study coordinators. This trial was registered under ClinicalTrials.gov Identifier: NCT01281150.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 241 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Malhotra, M.K., Pahuja, S., Kiesel, B.F. et al. A phase 1 study of veliparib (ABT-888) plus weekly carboplatin and paclitaxel in advanced solid malignancies, with an expansion cohort in triple negative breast cancer (TNBC) (ETCTN 8620). Breast Cancer Res Treat 198, 487–498 (2023). https://doi.org/10.1007/s10549-023-06889-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1007/s10549-023-06889-0

Keywords