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Review

Experimental drugs for fallopian cancer: promising agents in the clinical trials and key stumbling blocks for researchers

, , , , , , , , & show all
Pages 1339-1357 | Received 29 Jul 2022, Accepted 15 Dec 2022, Published online: 28 Dec 2022

References

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  • Phase 2 study of pembrolizumab, DPX-survivac vaccine and cyclophosphamide in advanced ovarian, primary peritoneal or fallopian tube cancer (2018, 2024) (NCT03029403.
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  • A randomized phase 2 trial of atezolizumab (MPDL3280A), SGI-110 and CDX-1401 vaccine in recurrent ovarian cancer (NCT03206047).
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  • A phase III randomised, double-blind, placebo-controlled, multicentre study of durvalumab in combination with chemotherapy and bevacizumab, followed by maintenance durvalumab, bevacizumab and olaparib in newly diagnosed advanced ovarian cancer patients (DUO-O). NCT03737643.
  • Phase II study of ipilimumab monotherapy in recurrent platinum-sensitive ovarian cancer-study results.
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  • A single-arm phase II study of niraparib and bevacizumab maintenance therapy in platinum-sensitive recurrent ovarian cancer patients previously treated with a PARP inhibitor (NCT04734665).
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  • ENGOT-0V44 The FIRST (First-line ovarian cancer treatment with niraparib plus TSR-042) study: a randomized, double-blind, phase 3 comparison of platinum-based therapy with TSR-042 and niraparib versus standard of care platinum-based therapy as first-line treatment of Stage III or IV. Nonmucinous Epithelial Ovarian Cancer (NCT03602859.
  • A phase Ib study of the oral PARP inhibitor niraparib with the intravenous PI3K inhibitor copanlisib for recurrent endometrial and recurrent ovarian, primary peritoneal, or fallopian tube cancer (2019-2022).
  • Lui GYL, Shaw R, Schaub FX, et al. BET, SRC, and BCL2 family inhibitors are synergistic drug combinations with PARP inhibitors in ovarian cancer. EBioMedicine. 2020 Oct;60:102988. Epub 2020 Sep 11. PMID: 32927276; PMCID: PMC7494677 doi: 10.1016/j.ebiom.2020.102988
  • Phase ll study of a BET inhibitor, ZEN003694, combined with a PARP inhibitor, talazoparib, in patients with recurrent ovarian cancer. NCT05071937.
  • BrUOG 390: neoadjuvant treatment with talazoparib for women with newly diagnosed, advanced ovarian cancer associated with a mutation in BRCA1 or BRCA2 (mBRCA) (2021-2027). NCT04598321.
  • NOW. Neoadjuvant olaparib window trial in newly diagnosed BRCA-mutant ovarian cancer. (NCT03943173). 2019-2022 [cited 2022 Dec 5]. https://www.clinicaltrials.gov/ct2/show/NCT03943173
  • Niraparib maintenance in patients with advanced ovarian cancer at neoadjuvant setting - a phase 2, single-arm trial (NEOPRIMA Trial). NCT04284852.
  • The NUVOLA TRIAL: neoadjuvant chemotherapy in unresectable oVarian cancer with OLAparib and weekly carboplatin plus paclitaxel: a phase II open-label multicentre study (NCT04261465).
  • Aithal A, Rauth S, Kshirsagar P, et al. MUC16 as a novel target for cancer therapy. Expert Opin Ther Targets. 2018;22(8):675–686.
  • Lee D-H, Choi S, Park Y, et al. Mucin1 and Mucin16: therapeutic targets for cancer therapy. Pharmaceuticals. 2021;14(10):1053.
  • Berek JS, Taylor PT, Gordon A, et al. Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer. J Clin Oncol. 2004;22(17):3507–3516.
  • Berek J, Taylor P, McGuire W, et al. Oregovomab maintenance monoimmunotherapy does not improve outcomes in advanced ovarian cancer. J Clin Oncol. 2009;27(3):418–425.
  • A double-blind, placebo-controlled, multicenter clinical trial of intravenous OvaRex® MAb-B43.13 as post chemotherapy consolidation for epithelial carcinoma of ovarian, tubal or peritoneal origin. (NCT00050375).
  • Battaglia A, Buzzonetti A, Fossati M, et al. Translational immune correlates of indirect antibody immunization in a randomized phase II study using scheduled combination therapy with carboplatin/paclitaxel plus oregovomab in ovarian cancer patients. Cancer Immunol Immunother. 2020;69(3):383–397.
  • A multicenter phase 3, double-blind, placebo-controlled study comparing chemo-immunotherapy (paclitaxel-carboplatin- oregovomab) vs chemotherapy (paclitaxel-carboplatin- placebo) in patients with advanced epithelial ovarian, fallopian tube or peritoneal carcinoma. (NCT04498117), FLORA-5. (2020-2027). https://clinicaltrials.gov/ct2/show/NCT04498117
  • Phase 1b/2, single arm clinical trial to evaluate the safety and activity of oregovomab and bevacizumab, paclitaxel carboplatin as a combinatorial strategy in subjects with BRCA-wild type platinum sensitive recurrent ovarian cancer. NCT04938583.
  • A phase Ib/IIa clinical trial to evaluate the safety and activity of oregovomab and nivolumab as a combinatorial immunotherapy strategy in patients with recurrent epithelial cancer of ovarian, tubal or peritoneal origin. NCT03100006.
  • A phase I/II clinical trial to evaluate platinum-based chemotherapy, oregovomab and nivolumab in patients with platinum sensitive recurrent epithelial cancer of ovarian, tubal or peritoneal origin. NCT04620954.
  • Phase 2, single arm clinical trial to evaluate the safety and activity of oregovomab and niraparib as a combinatorial immune priming strategy in subjects with platinum sensitive. Recurrent Ovarian Cancer (NCT05335993.
  • A phase II study of oregovomab and PLD in PARP inhibitor resistant ovarian, fallopian tube, or primary peritoneal cancer patients not candidate for platinum retreatment. NCT05407584.
  • Phase 1/2 study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific) administered in combination with cemiplimab or REGN4018 (MUC16xCD3) (2020-2026). NCT04590326.
  • A phase 1/2 Study of REGN4018 (A MUC16xCD3 Bispecific Antibody) administered alone or in combination with cemiplimab in patients with recurrent ovarian cancer (2018-2024). NCT03564340.
  • Kong A, Mehanna H. WEE1 inhibitor: clinical development. Curr Oncol Rep. 2021 Jul 16;23(9):107. PMID: 34269904; PMCID: PMC8285350.
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  • A randomized placebo-controlled phase II trial comparing gemcitabine monotherapy to gemcitabine in combination with AZD 1775 (MK 1775) in women with recurrent, platinum resistant epithelial ovarian, primary peritoneal, or fallopian tube cancers. ((NCT02151292.
  • Oza AM, Estevez-Diz M, Grischke EM, et al. A biomarker-enriched, randomized phase II trial of adavosertib (AZD1775) plus paclitaxel and carboplatin for women with platinum-sensitive TP53-mutant ovarian cancer. Clin Cancer Res. 2020 Sep 15;26(18):4767–4776. Epub 2020 Jul 1. PMID: 32611648.
  • EFFORT. Efficacy of AZD1775 in Parp resistance; A randomized 2-arm, non-comparative phase 2 study of AZD1775 Alone or AZD1775 and olaparib in women with ovarian cancer who have progressed during PARP inhibition. NCT03579316. [cited 2022 Dec 5]. https://clinicaltrials.gov/ct2/show/NCT03579316
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  • A phase 1/2 dose-escalation and dose-expansion study of ZN-c3 in combination with niraparib in subjects with platinum-resistant ovarian cancer. NCT05198804.
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