Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Matheus Sewastjanow-Silva
 -- 1537 2023-10-30 14:40:22 |
2 Format correct
Wendy Huang
 -2 word(s) 1535 2023-10-31 05:22:40 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Rogers, J.E.; Yamashita, K.; Sewastjanow-Silva, M.; Trail, A.; Waters, R.E.; Ajani, J. Newer HER2 Therapies for Gastric Adenocarcinomas. Encyclopedia. Available online: https://encyclopedia.pub/entry/50939 (accessed on 01 August 2024).
Rogers JE, Yamashita K, Sewastjanow-Silva M, Trail A, Waters RE, Ajani J. Newer HER2 Therapies for Gastric Adenocarcinomas. Encyclopedia. Available at: https://encyclopedia.pub/entry/50939. Accessed August 01, 2024.
Rogers, Jane E., Kohei Yamashita, Matheus Sewastjanow-Silva, Allison Trail, Rebecca E. Waters, Jaffer Ajani. "Newer HER2 Therapies for Gastric Adenocarcinomas" Encyclopedia, https://encyclopedia.pub/entry/50939 (accessed August 01, 2024).
Rogers, J.E., Yamashita, K., Sewastjanow-Silva, M., Trail, A., Waters, R.E., & Ajani, J. (2023, October 30). Newer HER2 Therapies for Gastric Adenocarcinomas. In Encyclopedia. https://encyclopedia.pub/entry/50939
Rogers, Jane E., et al. "Newer HER2 Therapies for Gastric Adenocarcinomas." Encyclopedia. Web. 30 October, 2023.
Newer HER2 Therapies for Gastric Adenocarcinomas
Edit
This entry is adapted from the peer-reviewed paper 10.3390/cancers15215180

Human epidermal growth factor receptor-2 (HER2) is a well-known target for approximately 15% of gastric adenocarcinomas (GACs). Although a plethora of HER2-targeted agents are marketed, currently only two agents are approved for GAC. These two agents are used only in the metastatic setting. Trastuzumab is utilized in combination with front-line chemotherapy, and trastuzumab deruxtecan is given following failure of trastuzumab therapy.

human epidermal growth factor receptor-2 trastuzumab trastuzumab deruxtecan ZW25 margetuximab antibody drug conjugates (ADCs) gastric adenocarcinomas

1. Introduction

Metastatic gastric adenocarcinomas (GACs) carry a poor prognosis with limited therapy options after first-line failure [1]. Some GACs (~15%) over-express human epidermal growth factor receptor-2 (HER2), making them candidates for HER2-targeted therapy. According to the guidelines, HER2 over-expressing GACs are classified by HER2 protein 3+ via immunohistochemistry (IHC), HER2 protein 2+ via IHC+ with an ERBB2/CEP17 ratio ≥ 2 using fluorescence in situ hybridization (FISH), or an average of ERBB2 copy number ≥ 6 signals/cell. Newer HER2 therapies are challenging these designations by exploring effectiveness in those with lower expression (or assessments using other platforms such as liquid biopsy or Next Gen Sequencing). This research focuses on the current understanding of HER2 agents in HER2-positive advanced GAC management. 

2. Antibody Drug Conjugates (ADCs)

ADCs are a novel drug design in which antibodies are chemically linked to cytotoxic therapy [2][3][4][5]. The antibody component exerts its anti-tumor effects by recognizing the antigen on the target cells, facilitating the formation of an antigen–antibody conjugate, which allows the cytotoxic payload to be rapidly internalized, leading to release of the cytotoxic component [5]. Ideally, this mechanism should reduce off-target toxicity; however, as mentioned previously, trastuzumab deruxtecan, an ADC that consists of trastuzumab with a topoisomerase inhibitor, carries substantial toxicity [6][7]. The hope is that newer generations of ADCs and continued development in this area will yield safer agents. Additional HER2 ADCs are being explored in HER2-positive GAC. RC48 is an ADC composed of hertuzumab, an anti-HER2 mAb conjugated to a microtubule inhibitor, monomethylauristatin E (MMAE) [8][9]. A phase 2 trial in ICH 2+/3+ advanced GAC patients in the refractory setting showed an ORR of 24.8%, median PFS of 4.1 months, and median OS of 7.9 months [5][8][9]. Those with HER2 IHC 2+/FISH− showed an ORR of 16.7%. Of note, RC48 was approved in China for GAC. Phase 3 in this population is under investigation using NCT04714190 [10]. Other HER2 ADCs are being explored in solid tumors. Preliminary results of ZW49 (auristatin) in heavily pretreated HER2-positive solid tumor patients showed an ORR of 31% with disease control of 72% [11][12]. For the GAC patients (n = 11), the ORR was 37% with a disease control rate of 73%. ARX788 (amberstatin conjugate) showed encouraging phase 1 results in HER2 refractory GAC patients (n = 30) with an ORR of 37.9%, disease control of 55.2%, median PFS of 4.1 months, and median OS of 10.7 months [13]. ARX788 was granted orphan drug status with the FDA in 2021 [14]. Examples along with their cytotoxic payload include MRG002 (microtubule disrupting agent monomethyl auristatin E), SYD985 (duocarmyicin), PF-06804103 (Aur0101), FS-1502 (monomethyl auristatin F), GQ1001 (DM1), A166 (microtubule cytotoxic agent), XMT-1522 (auristatin), BDC-1001 (toll-like receptor), ALT-P7 (monomethyl auristatin E), and SBT6050 (toll-like receptor) [2][4][5]. Trial examples of these agents are described in Table 1 [10][15][16][17][18][19][20][21][22][23].
Table 1. HER2-targeted antibody-drug conjugate examples currently under investigation [10][15][16][17][18][19][20][21][22][23].
Drug Name HER2 bsAb Trial Number Phase Population
RC48 Anti-HER2 + MMAE NCT04714190
NCT05514158
NCT05982834		 3
1
1/2		 Locally advanced/metastatic HER2 GAC
Locally advanced/metastatic HER2 GAC
Metastatic HER2 GAC
ZW49 Anti-HER2 bsAb (ZW25) + Auristatin NCT03821233 1 Advanced HER2-expressing cancers
MRG002 Anti-HER2 IgG1 + MMAE NCT04492488
NCT05141747		 1
2		 Advanced HER2 solid tumors
Locally advanced/metastatic HER2-positive/HER2 low GAC
FS-1502 Anti-HER2 + MMAF NCT03944499 1 HER2-positive advanced breast or solid tumors
GQ1001 Anti-HER2 + DM1 NCT04450732 1 HER2-positive advanced solid tumors
ARX788 Modified Trastuzumab + MMAF NCT03255070 1 HER2-positive advanced solid tumors
BDC-1001 Trastuzumab biosimilar + TLR7/8 agonist NCT04278144 1/2 HER2-positive advanced solid tumors
bsAb (bispecific antibody); HER2: human epidermal growth factor receptor-2.

3. Antibodies

Zanidatamab (ZW25), a HER2-targeted bispecific antibody, has emerged as a promising therapy. It binds to two extracellular domains of HER2, extracellular domain IV and II. These are the same domains targeted by trastuzumab and pertuzumab, respectively. Meric-Bernstam et al. published phase 1 results in HER2 IHC 3+ or 2+ advanced refractory (median prior therapies = 2–3) GACs [24]. Parts 1 and 2 were given single-agent zanidatamab (n = 36), whereas part 3 (n = 26) utilized zanidatamab in combination with a fluoropyrimidine or a taxane. Most patients had prior HER2 therapies (>90%). The ORR was 38% for the single-agent parts and 60% for zanidatamab + chemotherapy, with a median duration of response of 6 months (95% CI 1.9–9.2 months) and 8.9 months (95% CI 3.5-NE months), respectively. Ku et al. reported preliminary results on phase 2 of zanidatamab in combination with front-line fluoropyrimidine plus platinum HER2 IHC 3+ or IHC 2+/FISH + advanced GAC [25]. For 28 patients, the outcomes showed a benefit (75% ORR, median duration of response of 16.4 months, and median PFS of 12 months). Further evaluations are underway with NCT03929666, a phase 2 trial with zanidatamab + chemotherapy, and HERIZON-GEA-01, a phase 3 trial with zanidatamab + chemotherapy +/− tislelizumab, an anti-PD-I antibody [26][27]. Of note, preliminary results of NCT03929666 have shown remarkable outcomes thus far. Zanidatamab + chemotherapy (CapeOx, FOLFOX, 5-FU + cisplatin) (n = 38) achieved an ORR of 79%, and 13% had stable disease, showing a disease control rate of 92% with a median duration of response of 20.4 months [28]. The median PFS was 12.5 months and median OS was NE. The 12-month OS was 88% and 18-month OS was 84%. Results of phase 3 HERIZON-GEA-01 [27] are looked forward to.
Margetuximab, a HER2 mAb similar to trastuzumab, has been engineered to increase affinity for the stimulatory Fc receptor (CD16A) and decrease affinity for the inhibitory Fc receptor (CD32B) on natural killer cells to increase antibody-dependent cellular cytotoxic response [29][30]. In vitro, margetuximab enhances the PD-1/PD-L1 axis expression and LAG-3 on natural killer and NK T cells. Blocking PD-1 would, in theory, enhance margetuximab NK cell activation, proliferation, and cytotoxicity. CP-MGAH22-05, a multicenter phase 1b/2 trial, combined margetuximab with pembrolizumab in refractory (1–2 previous therapies) HER2 IHC 3+ or IHC 2+/FISH+ advanced GAC (n = 95) [29]. PD-L1 expression was not an inclusion criterion but was explored (expression considered CPS ≥ 1). Overall outcomes were 18% ORR, median PFS of 2.73 months, and median OS of 12.48 months. HER2 amplification by ctDNA was associated with better ORR (HER2 amplification 31% ORR vs. HER2 amplification negative 6% ORR). Those with both HER2 IHC 3+ and PD-L1 expression also showed an ORR of 44%, and those with HER2 amplification by ctDNA with PD-L1 expression showed an ORR of 50%. The role of ctDNA in outcomes poses a unique question, namely whether following ctDNA expression during HER2 therapy may hold keys to establishing patients who can truly benefit. Interim analysis (n = 43) of the MAHOGANY trial, a phase 2/3 trial, was reported on the combination of margetuximab + retifanlimab, anti-PD-1 mAb, given as a front-line treatment for HER2 IHC 3+ and PD-L1 positive patients [31]. The best ORR was 52.5% with a median PFS of 6.4 months. MAHOGANY is also exploring the combination of margetuximab +/− tebotelimab, anti-LAG-3, and anti-PD-1 mAb [30].
KN026, a bispecific HER2 mAb targeting extracellular domains IV and II, has shown activity. Xu et al. showed phase 2 activity in two cohorts (cohort 1 (n = 25): IHC 3+ or IHC 2+/FISH +; cohort 2 (n = 14): IHC 0/1 +; FISH +) of refractory GAC and GEJ adenocarcinoma patients (≥one prior therapy) [32]. Cohort 1 reported an ORR of 55.6%, median PFS of 8.3 months, and median OS of 16.3 months. Of note, activity was seen in those that received prior HER2 therapy. Cohort 2 (n = 14) showed a minimal signal with 14% ORR, median PFS of 1.4 months, and median OS of 9.6 months, strengthening the importance of patient identification for trials. Dong et al. reported results of KN026 with KN046, anti-CTLA4/PD-L1 mAb in phase 1b GAC patients (n = 47). Eligibility included HER2 alterations (low expression, overexpression, mutation, or amplification), in naïve or refractory treatment. The ORR was 71.4% in the treatment naïve group and 37.5% in the refractory group. No response was seen in those with low HER2 expression or mutations. Of note, activity was still present in those that had prior HER2 and PD-1 agents. NCT05427383 is a current phase 2/3 trial evaluating KN046 in combination with chemotherapy (taxane or irinotecan) in the second-line HER2-positive advanced GAC [33].

4. Other Strategies

Promising results reported by ASPEN-01, a phase 1 trial, on ALX148, a CD47 inhibitor, show novel combination strategies [34]. ASPEN-01 studied the combination of ALX148 + trastuzumab (n = 20) or ALX148 + trastuzumab + ramucirumab + paclitaxel (n = 18) in the second-line setting for HER2-positive advanced GAC patients. Most patients had prior HER2-targeted agent exposure. The ORR was 72% in the arm with ramucirumab plus paclitaxel, and the ALX148 and trastuzumab arm ORR was 21%. ALX148 + trastuzumab + ramucirumab + paclitaxel is being evaluated in ASPEN-06, a phase 2/3 trial, in advanced HER2-positive GAC patients [35]. NCT05027139 is looking at ALX148 with ZW25 in HER2-positive solid tumor patients [36]. Triplet combinations with HER2 kinase inhibitors in combination with chemotherapy and PD-1 inhibition are also being explored, such as in NCT05111444 [37]. Additionally, studies of vaccine and chimeric antigen receptor T-cell (CART) HER2 targets are underway. Oral HER2 tyrosine kinase combination studies are also underway, including MOUNTAINEER-02, which is studying tucatinib in combination with trastuzumab, ramucirumab, and paclitaxel compared to ramucirumab and paclitaxel alone in the refractory setting [38].
Chen et al. recently published five potential hub genes that contribute to GAC [39]. The researchers used gene expression profiles and an RNA-sequencing dataset of GAC acquired from the Gene Expression Omnibus dataset and The Cancer Genome Atlas dataset. Ten important gene sets associated with resistance were identified. Linking these discoveries with clinical practice is necessary for further success. More understanding in this area will lead to advancements in HER2 resistance.

References

  1. National Comprehensive Cancer Network. Gastric Cancer. Version 2. 2022. Available online: https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf (accessed on 28 October 2022).
  2. Fong, C.; Chau, I. HER2 Inhibition in Gastric Cancer—Novel Therapeutic Approaches for an Established Target. Cancers 2022, 14, 3824.
  3. Blangé, D.; Stroes, C.I.; Derks, S.; Bijlsma, M.F.; van Laarhoven, H.W. Resistance mechanisms to HER2-targeted therapy in gastroesophageal adenocarcinoma: A systematic review. Cancer Treat. Rev. 2022, 108, 102418.
  4. Díaz-Rodríguez, E.; Gandullo-Sánchez, L.; Ocaña, A.; Pandiella, A. Novel ADCs and Strategies to Overcome Resistance to Anti-HER2 ADCs. Cancers 2021, 14, 154.
  5. Zhu, Y.; Zhou, M.; Kong, W.; Li, C. Antibody-drug conjugates: The clinical development in gastric cancer. Front. Oncol. 2023, 13, 1211947.
  6. Yamaguchi, K.; Bang, Y.J.; Iwasa, S.; Sugimoto, N.; Ryu, M.H.; Sakai, D.; Chung, H.C.; Kawakami, H.; Yabusaki, H.; Lee, J.; et al. Trastuzumab deruxtecan in anti-human epidermal growth factor receptor 2 treat-ment-naïve patients with human epidermal growth factor receptor 2-low gastric or gastroesophageal junction adenocarcinoma: Exploratory cohort results in a phase II trial. J. Clin. Oncol. 2023, 41, 816–825.
  7. Van Cutsem, E.; di Bartolomeo, M.; Smyth, E.; Chau, I.; Park, H.; Siena, S.; Lonardi, S.; Wainberg, Z.A.; Ajani, J.; Chao, J.; et al. Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): Primary and updated analyses from a single-arm, phase 2 study. Lancet Oncol. 2023, 24, 744–756.
  8. Peng, Z.; Liu, T.; Wei, J.; Wang, A.; He, Y.; Yang, L.; Zhang, X.; Fan, N.; Luo, S.; Li, Z.; et al. Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: A single-arm phase II study. Cancer Commun. 2021, 41, 1173–1182.
  9. Yu, M.; Liang, Y.; Li, L.; Zhao, L.; Kong, F. Research progress of antibody-drug conjugates therapy for HER2-low expressing gastric cancer. Transl. Oncol. 2023, 29, 101624.
  10. RemeGen Co., Ltd. A Study of RC48-ADC in Local Advanced or Metastatic Gastric Cancer with the HER2-Overexpression. Bethesda (MD): National Library of Medicine (US). 2000. Available online: https://clinicaltrials.gov/ct2/show/NCT04714190 (accessed on 25 October 2023).
  11. Jhaveri, K.; Han, H.; Dotan, E.; Oh, D.-Y.; Ferrario, C.; Tolcher, A.; Lee, K.-W.; Liao, C.-Y.; Kang, Y.-K.; Kim, Y.; et al. 460MO Preliminary results from a phase I study using the bispecific, human epidermal growth factor 2 (HER2)-targeting antibody-drug conjugate (ADC) zanidatamab zovodotin (ZW49) in solid cancers. In Proceedings of the Annual Meeting of the European-Society-for-Medical-Oncology (ESMO), Madrid, Spain, 20–24 October 2023; pp. S749–S750.
  12. Zymeworks Press Release. Zymeworks Reports Preliminary Phase 1 Trial Results for Zanidatamab Zovodotin (ZW49) at European Society for Medical Oncology Annual Congress. Available online: https://ir.zymeworks.com/news-releases/news-release-details/zymeworks-reports-preliminary-phase-1-trial-results-zanidatamab (accessed on 21 August 2023).
  13. Zhang, Y.; Qiu, M.-Z.; Wang, J.-F.; Zhang, Y.-Q.; Shen, A.; Yuan, X.-L.; Zhang, T.; Wei, X.-L.; Zhao, H.-Y.; Wang, D.-S.; et al. Phase 1 multicenter, dose-expansion study of ARX788 as monotherapy in HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma. Cell Rep. Med. 2022, 3, 100814.
  14. Ambrx Granted Orphan Drug Designation for ARX788 for the Treatment of Gastric Cancer. Available online: https://ambrx.com/news/ambrx-granted-orphan-drug-designation-for-arx788-for-the-treatment-of-gastric-cancer/ (accessed on 17 March 2021).
  15. RemeGen Co., Ltd. To Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Disitamab Vedotin Combined with RC98 in the Treatment of Subjects with HER2-Expressing Locally Advanced or Metastatic Gastric Cancer (Including AEG). NLM Identi-Fier: NCT05514158. Available online: https://clinicaltrials.gov/study/NCT05514158 (accessed on 25 October 2023).
  16. Fudan University. Disitamab Vedotin, Fruquintinib and Tislelizumab in Second-Line Treatment for HER2-Positive MGC. NLM Identifier: NCT05982834. Available online: https://clinicaltrials.gov/study/NCT05982834 (accessed on 25 October 2023).
  17. Zymeworks Inc. A Dose Finding Study of ZW49 in Patients with HER2-Positive Cancers. Available online: https://clinicaltrials.gov/ct2/show/NCT03821233 (accessed on 25 October 2023).
  18. Shanghai Miracogen Inc. A Study of MRG002 in Patients with HER2-Positive Advanced Solid Tumors and Locally Advanced or Metastatic Gastric/Gastroesophageal Junction (GEJ) Cancer. Available online: https://clinicaltrials.gov/ct2/show/NCT04492488 (accessed on 25 October 2023).
  19. Shanghai Miracogen Inc. A Study of MRG002 in the Treatment of HER2-Positive/HER2-Low Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Cancer. Available online: https://clinicaltrials.gov/ct2/show/NCT05141747 (accessed on 25 October 2023).
  20. Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd. Phase 1 Study of FS-1502 in Patients with HER2 Expressed Advanced Solid Tumors and Breast Cancer. Available online: https://clinicaltrials.gov/ct2/show/NCT03944499 (accessed on 25 October 2023).
  21. GeneQuantum Healthcare (Suzhou) Co., Ltd. Safety of GQ1001 in Adult Patients with HER2-Positive Advanced Solid Tumors. Available online: https://clinicaltrials.gov/ct2/show/NCT04450732 (accessed on 25 October 2023).
  22. Ambrx, Inc. A Dose-escalation, Expansion Study of ARX788, in Advanced Solid Tumors Subjects with HER2 Expression (ACE-Pan Tumor 01). Available online: https://clinicaltrials.gov/ct2/show/NCT03255070 (accessed on 25 October 2023).
  23. Bolt Biotherapeutics, Inc. A First-in-human Study Using BDC-1001 as a Single Agent and in Combination with Nivolumab in Advanced HER2-Expressing Solid Tumors. Available online: https://clinicaltrials.gov/ct2/show/NCT04278144 (accessed on 25 October 2023).
  24. Meric-Bernstam, F.; Hamilton, E.P.; Beeram, M.; Hanna, D.L.; El-Khoueiry, A.B.; Kang, Y.-K.; Lee, K.W.; Lee, J.; Rha, S.Y.; Chaves, J.M.; et al. Zanidatamab (ZW25) in HER2-expressing gastroesophageal adenocarcinoma (GEA): Results from a phase I study. J. Clin. Oncol. 2021, 39, 164.
  25. Ku, G.; Elimova, E.; Denlinger, C.; Mehta, R.; Lee, K.-W.; Iqbal, S.; Kang, Y.-K.; Oh, D.-Y.; Rha, S.; Kim, Y.; et al. 1380P Phase (Ph) II study of zanidatamab + chemotherapy (chemo) in first-line (1L) HER2 expressing gastroesophageal adenocarcinoma (GEA). In Proceedings of the Congress of the European-Society-for-Medical-Oncology (ESMO), Madrid, Spain, 20–24 October 2023; pp. S1044–S1045.
  26. Zymeworks Inc. A Safety and Efficacy Study of ZW25 (Zanidatamab) Plus Combination Chemotherapy in HER2-Expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer. Available online: https://clinicaltrials.gov/ct2/show/NCT03929666 (accessed on 25 October 2023).
  27. Tabernero, J.; Shen, L.; Elimova, E.; Ku, G.; Liu, T.; Shitara, K.; Lin, X.; Boyken, L.; Li, H.; Grim, J.; et al. HERIZON-GEA-01: Zanidatamab + chemo ± tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma. Futur. Oncol. 2022, 18, 3255–3266.
  28. Elimova, E.; Ajani, J.A.; Burris, I.I.I.H.A.; Denlinger, C.S.; Iqbal, S.; Kang, Y.K.; Kim, Y.H.; Lee, K.W.; Lin, B.; Mehta, R.; et al. Zanidatamab + chemotherapy as first-line treatment for HER2-expressing metastatic gas-troesophageal adenocarcinoma (mGEA). J. Clin. Oncol. 2023, 41 (Suppl. S4), 347.
  29. Catenacci, D.V.; Kang, Y.K.; Park, H.; Uronis, H.E.; Lee, K.W.; Ng, M.C.; Enzinger, P.C.; Park, S.H.; Gold, P.J.; Lacy, J.; et al. Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22–05): A single-arm, phase 1b–2 trial. Lancet Oncol. 2020, 21, 1066–1076.
  30. Catenacci, D.V.; Rosales, M.; Chung, H.C.; Yoon, H.H.; Shen, L.; Moehler, M.; Kang, Y.-K. MAHOGANY: Margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma. Futur. Oncol. 2021, 17, 1155–1164.
  31. Catenacci, D.V.; Kang, Y.K.; Yoon, H.H.; Shim, B.Y.; Kim, S.T.; Oh, D.Y.; Spira, A.I.; Ulahannan, S.V.; Avery, E.J.; Boland, P.M.; et al. Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A. ESMO Open 2022, 7, 100563.
  32. Xu, J.; Zhang, Y.; Wu, J.; Xu, N.; Ying, J.; Xiang, X.; Zhang, Y.; Wang, J.; Zhao, R.; Ye, F.; et al. The preliminary efficacy of KN026 (Anti-HER2 BsAb) in advanced gastric and gastroesophageal junction cancer patients with HER2 expression. J. Clin. Oncol. 2021, 39, e16005.
  33. Shanghai JMT-Bio Inc. KN026 in Combination with Chemotherapy in the Second Line Treatment of HER-2 Positive Advanced or Metastatic Gastric Cancer. Available online: https://clinicaltrials.gov/ct2/show/NCT05427383 (accessed on 25 October 2023).
  34. Chung, H.; Lee, K.; Kim, W.; Gainor, J.; Lakhani, N.; Chow, L.; Messersmith, W.; Fanning, P.; Squifflet, P.; Jin, F.; et al. SO-31 ASPEN-01: A phase 1 study of ALX148, a CD47 blocker, in combination with trastuzumab, ramucirumab and paclitaxel in patients with second-line HER2-positive advanced gastric or gastroesophageal junction cancer. In Proceedings of the 23rd ESMO World Congress on Gastrointestinal Cancer, Barcelona, Spain, 28 June–1 July 2023; pp. S215–S216.
  35. ALX Oncology Inc. A Study of Evorpacept (ALX148) in Patients with Advanced HER2+ Gastric Cancer (ASPEN-06). Available online: https://www.clinicaltrials.gov/ct2/show/NCT05002127 (accessed on 25 October 2023).
  36. Zymeworks Inc. A Study of Zanidatamab (ZW25) with Evorpacept (ALX148) in Patients with Advanced HER2-Expressing Cancer. Available online: https://clinicaltrials.gov/ct2/show/NCT05027139 (accessed on 25 October 2023).
  37. Fudan University. Camrelizumab Plus Pyrotinib Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma. Available online: https://clinicaltrials.gov/ct2/show/NCT05111444 (accessed on 25 October 2023).
  38. Catenacci, D.V.; Strickler, J.H.; Nakamura, Y.; Shitara, K.; Janjigian, Y.Y.; Barzi, A.; Bekaii-Saab, T.S.; Lenz, H.J.; Chung, H.C.; Tabernero, J.; et al. Mountaineer-02: Phase 2/3 study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastoesophagela junction adenocarcinoma-trial in progress. J. Clin. Oncol. 2022, 40, TPS371.
  39. Chen, F.; Wang, Y.; Zhang, X.; Fang, J. Five hub genes contributing to the oncogenesis and trastuzumab-resistance in gastric cancer. Gene 2023, 851, 146942.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Oncology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Jane E. Rogers
,
Kohei Yamashita
,
Matheus Sewastjanow-Silva
,
Allison Trail
,
Rebecca E. Waters
,
Jaffer Ajani
View Times: 247
Revisions: 2 times (View History)
Update Date: 31 Oct 2023
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback