Histology Agnostic Drug Development: An Updated Review
Simple Summary
Abstract
1. Introduction
2. Promises and Pitfalls of Histology-Agnostic Therapy
- I.
- Approval of pembrolizumab in patients with unresectable or metastatic dMMR/MSI-H cancers (May 2017)
- II.
- Approval of larotrectinib in patients with unresectable or metastatic NTRK gene fusion-positive cancers (November 2018)
- III.
- Approval of entrectinib in patients with unresectable or metastatic NTRK gene fusion-positive cancers (August 2019)
- IV.
- Approval of pembrolizumab approved for patients with unresectable or metastatic TMB-H cancers (16 June 2020)
- V.
- Approval of dostarlimab in patients with unresectable or metastatic dMMR cancers (August 2021)
- VI.
- Approval of dabrafenib plus trametinib approved for patients with unresectable or metastatic BRAFV600E positive cancers (June 2022)
- VII.
- Approval of selpercatinib in patients with unresectable or metastatic RET-positive cancers in patients ≥ 12 years (September 2022)
- VIII.
- Approval of trastuzumab deruxtecan approved for patients with unresectable or metastatic HER2-positive cancers (April 2024)
- IX.
- Approval of repotrectinib approved for NTRK-positive tumors (June 2024)
3. Challenges, Remaining Questions and Future Directions
- (a)
- Does one size fit all?
- (b)
- Are there any diagnostic challenges?
- (c)
- Does the tumor microenvironment (TME) play a role?
- (d)
- Does tumor neoantigen burden (TNB) predict immunotherapy outcomes?
- (e)
- What agnostic therapies are on the horizon?
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
Declaration of Generative AI and AI-Assisted Technologies in the Writing Process
References
- Mansinho, A.; Fernandes, R.M.; Carneiro, A.V. Histology-Agnostic Drugs: A Paradigm Shift-A Narrative Review. Adv. Ther. 2023, 40, 1379–1392. [Google Scholar] [CrossRef] [PubMed]
- Thein, K.Z.; Lemery, S.J.; Kummar, S. Tissue-Agnostic Drug Development: A New Path to Drug Approval. Cancer Discov. 2021, 11, 2139–2144. [Google Scholar] [CrossRef] [PubMed]
- U.S. Food and Drug Administration. FDA Grants Accelerated Approval to Pembrolizumab for First Tissue/Site Agnostic Indication. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-first-tissuesite-agnostic-indication (accessed on 12 March 2024).
- U.S. Food and Drug Administration. FDA Approves Larotrectinib for Solid Tumors with NTRK Gene Fusions. Available online: https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions-0 (accessed on 12 March 2024).
- U.S. Food and Drug Administration. FDA Approves Entrectinib for NTRK Solid Tumors and ROS-1 NSCLC. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-entrectinib-ntrk-solid-tumors-and-ros-1-nsclc (accessed on 12 March 2024).
- U.S. Food and Drug Administration. FDA Approves Pembrolizumab for Adults and Children with TMB-H Solid Tumors. Available online: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors (accessed on 12 March 2024).
- U.S. Food and Drug Administration. FDA Grants Accelerated Approval to Dostarlimab-Gxly for dMMR Advanced Solid Tumors. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-gxly-dmmr-advanced-solid-tumors (accessed on 12 March 2024).
- U.S. Food and Drug Administration. FDA Grants Accelerated Approval to Dabrafenib in Combination with Trametinib for Unresectable or Metastatic Solid Tumors with BRAF V600E Mutation. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dabrafenib-combination-trametinib-unresectable-or-metastatic-solid (accessed on 12 March 2024).
- U.S. Food and Drug Administration. FDA Approves Selpercatinib for Locally Advanced or Metastatic RET Fusion-Positive Solid Tumors. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-locally-advanced-or-metastatic-ret-fusion-positive-solid-tumors (accessed on 12 March 2024).
- U.S. Food and Drug Administration. FDA Grants Accelerated Approval to Fam-Trastuzumab Deruxtecan-Nxki for Unresectable or Metastatic HER2-Positive Solid Tumors. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2 (accessed on 12 March 2024).
- U.S. Food and Drug Administration. FDA Grants Accelerated Approval to Repotrectinib for Adult and Pediatric Patients with NTRK Gene Fusion-Positive Solid Tumors. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-repotrectinib-adult-and-pediatric-patients-ntrk-gene-fusion-positive (accessed on 12 March 2024).
- Le, D.T.; Kim, T.W.; Cutsem, E.V.; Geva, R.; Jäger, D.; Hara, H.; Burge, M.; O’Neil, B.; Kavan, P.; Yoshino, T.; et al. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability–High/Mismatch Repair–Deficient Metastatic Colorectal Cancer: KEYNOTE-164. J. Clin. Oncol. 2020, 38, 11–19. [Google Scholar] [CrossRef] [PubMed]
- Maio, M.; Ascierto, P.A.; Manzyuk, L.; Motola-Kuba, D.; Penel, N.; Cassier, P.A.; Bariani, G.M.; De Jesus Acosta, A.; Doi, T.; Longo, F.; et al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: Updated analysis from the phase II KEYNOTE-158 study. Ann. Oncol. 2022, 33, 929–938. [Google Scholar] [CrossRef] [PubMed]
- Geoerger, B.; Kang, H.J.; Yalon-Oren, M.; Marshall, L.V.; Vezina, C.; Pappo, A.; Laetsch, T.W.; Petrilli, A.S.; Ebinger, M.; Toporski, J.; et al. Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): Interim analysis of an open-label, single-arm, phase 1–2 trial. Lancet Oncol. 2020, 21, 121–133. [Google Scholar] [CrossRef]
- U.S. Food and Drug Administration. FDA Grants Full Approval to Pembrolizumab for Certain Adult and Pediatric Patients with Advanced MSI-H or dMMR Solid Tumors. Available online: https://ascopost.com/news/march-2023/fda-grants-full-approval-to-pembrolizumab-for-certain-adult-and-pediatric-patients-with-advanced-msi-h-or-dmmr-solid-tumors/ (accessed on 12 March 2024).
- Manea, C.A.; Badiu, D.C.; Ploscaru, I.C.; Zgura, A.; Bacinschi, X.; Smarandache, C.G.; Serban, D.; Popescu, C.G.; Grigorean, V.T.; Botnarciuc, V. A review of NTRK fusions in cancer. Ann. Med. Surg. 2022, 79, 103893. [Google Scholar] [CrossRef]
- Hong, D.S.; DuBois, S.G.; Kummar, S.; Farago, A.F.; Albert, C.M.; Rohrberg, K.S.; van Tilburg, C.M.; Nagasubramanian, R.; Berlin, J.D.; Federman, N.; et al. Larotrectinib in patients with TRK fusion-positive solid tumours: A pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020, 21, 531–540. [Google Scholar] [CrossRef]
- Hong, D.S.; Drilon, A.E.; Tan, D.S.-W.; Lin, J.J.; Kummar, S.; McDermott, R.S.; Berlin, J.; Italiano, A.; Lassen, U.N.; Leyvraz, S.; et al. Larotrectinib long-term efficacy and safety in adult patients (pts) with tropomyosin receptor kinase (TRK) fusion cancer. J. Clin. Oncol. 2023, 41, 3141. [Google Scholar] [CrossRef]
- Marcus, L.; Donoghue, M.; Aungst, S.; Myers, C.E.; Helms, W.S.; Shen, G.; Zhao, H.; Stephens, O.; Keegan, P.; Pazdur, R. FDA Approval Summary: Entrectinib for the Treatment of NTRK gene Fusion Solid Tumors. Clin. Cancer Res. 2021, 27, 928–932. [Google Scholar] [CrossRef]
- Cho, B.C.; Chiu, C.H.; Massarelli, E.; Buchschacher, G.L.; Goto, K.; Overbeck, T.R.; Loong, H.H.F.; Chee, C.E.; Garrido, P.; Dong, X.; et al. Updated efficacy and safety of entrectinib in NTRK fusion-positive non-small cell lung cancer. Lung Cancer 2024, 188, 107442. [Google Scholar] [CrossRef]
- Demetri, G.D.; De Braud, F.; Drilon, A.; Siena, S.; Patel, M.R.; Cho, B.C.; Liu, S.V.; Ahn, M.J.; Chiu, C.H.; Lin, J.J.; et al. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients with NTRK Fusion-Positive Solid Tumors. Clin. Cancer Res. 2022, 28, 1302–1312. [Google Scholar] [CrossRef] [PubMed]
- Marcus, L.; Fashoyin-Aje, L.A.; Donoghue, M.; Yuan, M.; Rodriguez, L.; Gallagher, P.S.; Philip, R.; Ghosh, S.; Theoret, M.R.; Beaver, J.A.; et al. FDA Approval Summary: Pembrolizumab for the Treatment of Tumor Mutational Burden–High Solid Tumors. Clin. Cancer Res. 2021, 27, 4685–4689. [Google Scholar] [CrossRef] [PubMed]
- Schumacher, T.N.; Schreiber, R.D. Neoantigens in cancer immunotherapy. Science 2015, 348, 69–74. [Google Scholar] [CrossRef]
- U.S. Food and Drug Administration. KEYTRUDA (Pembrolizumab) US Product Information. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125514s084lbl.pdf (accessed on 12 March 2024).
- Cicala, C.M.; Musacchio, L.; Scambia, G.; Lorusso, D. Dostarlimab: From preclinical investigation to drug approval and future directions. Hum. Vaccin. Immunother. 2023, 19, 2178220. [Google Scholar] [CrossRef]
- Subbiah, V.; Kreitman, R.J.; Wainberg, Z.A.; Gazzah, A.; Lassen, U.; Stein, A.; Wen, P.Y.; Dietrich, S.; de Jonge, M.J.A.; Blay, J.-Y.; et al. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: The phase 2 ROAR trial. Nat. Med. 2023, 29, 1103–1112. [Google Scholar] [CrossRef] [PubMed]
- Gouda, M.A.; Subbiah, V. Expanding the Benefit: Dabrafenib/Trametinib as Tissue-Agnostic Therapy for BRAF V600E–Positive Adult and Pediatric Solid Tumors. Am. Soc. Clin. Oncol. Educ. Book. 2023, 43, e404770. [Google Scholar] [CrossRef]
- Duke, E.S.; Bradford, D.; Marcovitz, M.; Amatya, A.K.; Mishra-Kalyani, P.S.; Nguyen, E.; Price, L.S.L.; Fourie Zirkelbach, J.; Li, Y.; Bi, Y.; et al. FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors. Clin. Cancer Res. 2023, 29, 3573–3578. [Google Scholar] [CrossRef]
- Bradford, D.; Larkins, E.; Mushti, S.L.; Rodriguez, L.; Skinner, A.M.; Helms, W.S.; Price, L.S.L.; Zirkelbach, J.F.; Li, Y.; Liu, J.; et al. FDA Approval Summary: Selpercatinib for the Treatment of Lung and Thyroid Cancers with RET Gene Mutations or Fusions. Clin. Cancer Res. 2021, 27, 2130–2135. [Google Scholar] [CrossRef]
- U.S. Food and Drug Administration. RETEVMO (Selpercatinib) US Product Information. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213246s000lbl.pdf (accessed on 12 March 2024).
- Subbiah, V.; Drilon, A.E.; Sukrithan, V.; Spira, A.I.; Robinson, B.; Deschler-Baier, B.; Barker, S.; Lin, Y.; Szymczak, S.; Ohe, Y. Durable efficacy of selpercatinib in patients with RET fusion+ solid tumors, with a focus on GI tumors: LIBRETTO-001. J. Clin. Oncol. 2024, 42, 746. [Google Scholar] [CrossRef]
- Yan, M.; Schwaederle, M.; Arguello, D.; Millis, S.Z.; Gatalica, Z.; Kurzrock, R. HER2 expression status in diverse cancers: Review of results from 37,992 patients. Cancer Metastasis Rev. 2015, 34, 157–164. [Google Scholar] [CrossRef]
- Meric-Bernstam, F.; Makker, V.; Oaknin, A.; Oh, D.Y.; Banerjee, S.; González-Martín, A.; Jung, K.H.; Ługowska, I.; Manso, L.; Manzano, A.; et al. Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial. J. Clin. Oncol. 2024, 42, 47–58. [Google Scholar] [CrossRef] [PubMed]
- Smit, E.F.; Felip, E.; Uprety, D.; Nagasaka, M.; Nakagawa, K.; Paz-Ares Rodríguez, L.; Pacheco, J.M.; Li, B.T.; Planchard, D.; Baik, C.; et al. Trastuzumab deruxtecan in patients with metastatic non-small-cell lung cancer (DESTINY-Lung01): Primary results of the HER2-overexpressing cohorts from a single-arm, phase 2 trial. Lancet Oncol. 2024, 25, 439–454. [Google Scholar] [CrossRef] [PubMed]
- Siena, S.; Di Bartolomeo, M.; Raghav, K.; Masuishi, T.; Loupakis, F.; Kawakami, H.; Yamaguchi, K.; Nishina, T.; Fakih, M.; Elez, E.; et al. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): A multicentre, open-label, phase 2 trial. Lancet Oncol. 2021, 22, 779–789. [Google Scholar] [CrossRef] [PubMed]
- Abuhelwa, Z.; Alloghbi, A.; Alqahtani, A.; Nagasaka, M. Trastuzumab Deruxtecan-Induced Interstitial Lung Disease/Pneumonitis in ERBB2-Positive Advanced Solid Malignancies: A Systematic Review. Drugs 2022, 82, 979–987. [Google Scholar] [CrossRef] [PubMed]
- National Cancer Institute. Repotrectinib Expands Treatment Options for Lung Cancers with ROS1 Fusions. Available online: https://www.cancer.gov/news-events/cancer-currents-blog/2024/repotrectinib-lung-cancer-ros1#:~:text=FDA%20approved%20the%20drug%20in,treatment%20for%20ROS1%2Dpositive%20NSCLC.&text=In%20November%202023%2C%20the%20Food,called%20a%20ROS1%20gene%20fusion (accessed on 12 March 2024).
- Drilon, A.; Ou, S.-H.I.; Cho, B.C.; Kim, D.-W.; Lee, J.; Lin, J.J.; Zhu, V.W.; Ahn, M.-J.; Camidge, D.R.; Nguyen, J.; et al. Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations. Cancer Discov. 2018, 8, 1227–1236. [Google Scholar] [CrossRef]
- Pribluda, A.; de la Cruz, C.C.; Jackson, E.L. Intratumoral Heterogeneity: From Diversity Comes Resistance. Clin. Cancer Res. 2015, 21, 2916–2923. [Google Scholar] [CrossRef]
- Vranic, S.; Basu, G.D.; Hall, D.W.; Gatalica, Z. Tumor-Type Agnostic, Targeted Therapies: BRAF Inhibitors Join the Group. Acta Med. Acad. 2022, 51, 217–231. [Google Scholar] [CrossRef]
- Vellano, C.P.; White, M.G.; Andrews, M.C.; Chelvanambi, M.; Witt, R.G.; Daniele, J.R.; Titus, M.; McQuade, J.L.; Conforti, F.; Burton, E.M.; et al. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy. Nature 2022, 606, 797–803. [Google Scholar] [CrossRef]
- Alkholifi, F.K.; Alsaffar, R.M. Dostarlimab an Inhibitor of PD-1/PD-L1: A New Paradigm for the Treatment of Cancer. Medicina 2022, 58, 1572. [Google Scholar] [CrossRef]
- Litchfield, K.; Reading, J.L.; Puttick, C.; Thakkar, K.; Abbosh, C.; Bentham, R.; Watkins, T.B.K.; Rosenthal, R.; Biswas, D.; Rowan, A.; et al. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell 2021, 184, 596–614.e514. [Google Scholar] [CrossRef]
- Li, A.Y.; McCusker, M.G.; Russo, A.; Scilla, K.A.; Gittens, A.; Arensmeyer, K.; Mehra, R.; Adamo, V.; Rolfo, C. RET fusions in solid tumors. Cancer Treat. Rev. 2019, 81, 101911. [Google Scholar] [CrossRef] [PubMed]
- Schettini, F.; Prat, A. Dissecting the biological heterogeneity of HER2-positive breast cancer. Breast 2021, 59, 339–350. [Google Scholar] [CrossRef]
- Nicolò, E.; Boscolo Bielo, L.; Curigliano, G.; Tarantino, P. The HER2-low revolution in breast oncology: Steps forward and emerging challenges. Ther. Adv. Med. Oncol. 2023, 15, 17588359231152842. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Li, S.; Wang, Y.; Zhao, Y.; Li, Q. Protein tyrosine kinase inhibitor resistance in malignant tumors: Molecular mechanisms and future perspective. Signal Transduct. Target. Ther. 2022, 7, 329. [Google Scholar] [CrossRef]
- Liu, F.; Wei, Y.; Zhang, H.; Jiang, J.; Zhang, P.; Chu, Q. NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance. Front. Oncol. 2022, 12, 864666. [Google Scholar] [CrossRef] [PubMed]
- Román-Gil, M.S.; Pozas, J.; Rosero-Rodríguez, D.; Chamorro-Pérez, J.; Ruiz-Granados, Á.; Caracuel, I.R.; Grande, E.; Molina-Cerrillo, J.; Alonso-Gordoa, T. Resistance to RET targeted therapy in Thyroid Cancer: Molecular basis and overcoming strategies. Cancer Treat. Rev. 2022, 105, 102372. [Google Scholar] [CrossRef]
- Vivekanandhan, S.; Knutson, K.L. Resistance to Trastuzumab. Cancers 2022, 14, 5115. [Google Scholar] [CrossRef] [PubMed]
- Yaeger, R.; Corcoran, R.B. Targeting Alterations in the RAF-MEK Pathway. Cancer Discov. 2019, 9, 329–341. [Google Scholar] [CrossRef]
- Sharma, P.; Hu-Lieskovan, S.; Wargo, J.A.; Ribas, A. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell 2017, 168, 707–723. [Google Scholar] [CrossRef]
- Joyce, J.A.; Fearon, D.T. T cell exclusion, immune privilege, and the tumor microenvironment. Science 2015, 348, 74–80. [Google Scholar] [CrossRef]
- Sha, D.; Jin, Z.; Budczies, J.; Kluck, K.; Stenzinger, A.; Sinicrope, F.A. Tumor Mutational Burden as a Predictive Biomarker in Solid Tumors. Cancer Discov. 2020, 10, 1808–1825. [Google Scholar] [CrossRef] [PubMed]
- Budczies, J.; Seidel, A.; Christopoulos, P.; Endris, V.; Kloor, M.; Győrffy, B.; Seliger, B.; Schirmacher, P.; Stenzinger, A.; Denkert, C. Integrated analysis of the immunological and genetic status in and across cancer types: Impact of mutational signatures beyond tumor mutational burden. Oncoimmunology 2018, 7, e1526613. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, J.; Das, B.; Shin, S.; Chen, A. Challenges and Future Directions in the Management of Tumor Mutational Burden-High (TMB-H) Advanced Solid Malignancies. Cancers 2023, 15, 5841. [Google Scholar] [CrossRef]
- Merino, D.M.; McShane, L.M.; Fabrizio, D.; Funari, V.; Chen, S.J.; White, J.R.; Wenz, P.; Baden, J.; Barrett, J.C.; Chaudhary, R.; et al. Establishing guidelines to harmonize tumor mutational burden (TMB): In silico assessment of variation in TMB quantification across diagnostic platforms: Phase I of the Friends of Cancer Research TMB Harmonization Project. J. Immunother. Cancer 2020, 8, e000147. [Google Scholar] [CrossRef]
- Solomon, J.P.; Benayed, R.; Hechtman, J.F.; Ladanyi, M. Identifying patients with NTRK fusion cancer. Ann. Oncol. 2019, 30 (Suppl. S8), viii16–viii22. [Google Scholar] [CrossRef] [PubMed]
- Payandeh, M.; Sadeghi, M.; Sadeghi, E.; Janbakhsh, A. Is There any Concordance between of IHC with FISH in HER2-Positive Breast Cancer Patients? Int. J. Hematol. Oncol. Stem Cell Res. 2017, 11, 43–48. [Google Scholar]
- Dumbrava, E.E.I.; Balaji, K.; Raghav, K.; Hess, K.; Javle, M.; Blum-Murphy, M.; Ajani, J.; Kopetz, S.; Broaddus, R.; Routbort, M.; et al. Targeting ERBB2 (HER2) Amplification Identified by Next-Generation Sequencing in Patients with Advanced or Metastatic Solid Tumors Beyond Conventional Indications. JCO Precis. Oncol. 2019, 3, 1–12. [Google Scholar] [CrossRef]
- Xiao, Y.; Yu, D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol. Ther. 2021, 221, 107753. [Google Scholar] [CrossRef]
- Truffi, M.; Sorrentino, L.; Corsi, F. Fibroblasts in the Tumor Microenvironment. Adv. Exp. Med. Biol. 2020, 1234, 15–29. [Google Scholar] [CrossRef]
- Jiang, X.; Wang, J.; Deng, X.; Xiong, F.; Zhang, S.; Gong, Z.; Li, X.; Cao, K.; Deng, H.; He, Y.; et al. The role of microenvironment in tumor angiogenesis. J. Exp. Clin. Cancer Res. 2020, 39, 204. [Google Scholar] [CrossRef]
- Wang, P.; Chen, Y.; Wang, C. Beyond Tumor Mutation Burden: Tumor Neoantigen Burden as a Biomarker for Immunotherapy and Other Types of Therapy. Front. Oncol. 2021, 11, 672677. [Google Scholar] [CrossRef] [PubMed]
- Rizvi, N.A.; Hellmann, M.D.; Snyder, A.; Kvistborg, P.; Makarov, V.; Havel, J.J.; Lee, W.; Yuan, J.; Wong, P.; Ho, T.S.; et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science 2015, 348, 124–128. [Google Scholar] [CrossRef] [PubMed]
- Van Allen, E.M.; Miao, D.; Schilling, B.; Shukla, S.A.; Blank, C.; Zimmer, L.; Sucker, A.; Hillen, U.; Geukes Foppen, M.H.; Goldinger, S.M.; et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 2015, 350, 207–211. [Google Scholar] [CrossRef]
- Hong, D.S.; Fakih, M.G.; Strickler, J.H.; Desai, J.; Durm, G.A.; Shapiro, G.I.; Falchook, G.S.; Price, T.J.; Sacher, A.; Denlinger, C.S.; et al. KRAS(G12C) Inhibition with Sotorasib in Advanced Solid Tumors. N. Engl. J. Med. 2020, 383, 1207–1217. [Google Scholar] [CrossRef] [PubMed]
- Bekaii-Saab, T.S.; Yaeger, R.; Spira, A.I.; Pelster, M.S.; Sabari, J.K.; Hafez, N.; Barve, M.; Velastegui, K.; Yan, X.; Shetty, A.; et al. Adagrasib in Advanced Solid Tumors Harboring a KRASG12C Mutation. J. Clin. Oncol. 2023, 41, 4097–4106. [Google Scholar] [CrossRef]
- Pant, S.; Schuler, M.; Iyer, G.; Witt, O.; Doi, T.; Qin, S.; Tabernero, J.; Reardon, D.A.; Massard, C.; Minchom, A.; et al. Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): An international, single-arm, phase 2 study. Lancet. Oncol. 2023, 24, 925–935. [Google Scholar] [CrossRef]
Drug Name (s) | Approval Date (MM/DD/YYYY) | Indication | Clinical Trial (s) | Cohort (n) | Outcome Measures Used for Approval | Ref |
---|---|---|---|---|---|---|
Pembrolizumab | 05/23/2017 | MSI-H/dMMR solid tumors for adult and pediatric population | KEYNOTE-016,-164, -012, -028, and -158 | 149 | ORR = 39.6% (95% CI: 31.7, 47.9), CR = 11, PR = 48, 78% with DOR ≥ 6 months | [3] |
Larotrectinib | 11/26/2018 | NTRK fusion-positive solid tumors for adult and pediatric population | LOXO-TRK-1400, NAVIGATE, SCOUT | 55 | ORR = 75% (95% CI: 61, 85), CR = 22%, PR = 53%, mDOR = NR, 73% with DOR ≥ 6 months, 63% with DOR ≥ 9 months, 39% with DOR ≥ 12 months | [4] |
Entrectinib | 08/15/2019 | NTRK fusion-positive solid tumors for adult and pediatric population (12 years or older) | ALKA, STARTRK-1, STARTRK02 | 54 | ORR = 57% (95% CI: 43, 71), 68% with DOR ≥ 6 months, 45% with DOR ≥ 12 months | [5] |
Pembrolizumab | 06/15/2020 | TMB-H (≥10 mut/mb) solid tumors for adult and pediatric population | KEYNOTE-158 | 102 | ORR = 29% (95% CI: 21, 39), CR = 4%, PR = 25%, mDOR = NR, 57% with DOR ≥ 12 months. 50% with DOR ≥ 24 months | [6] |
Dostarlimab | 08/17/2021 | MSI-H/dMMR solid tumors for adult population | GARNET | 209 | ORR = 41.6% (95% CI: 34.9, 48.6), CR = 9.1%, PR = 32.5%, mDOR = 34.7 (2.6 to 35.8+) months, 95.4% with DOR ≥ 6 months | [7] |
Dabrafenib plus trametinib | 06/22/2022 | BRAF V600E solid tumors * for patients 6 years or older | BRF117019, NCI-MATCH, CTMT212X2101 | Adults: 131 Children: 36 | Adults: ORR = 41% (95% CI: 33, 50) Children: ORR = 25% (95% CI: 12, 42), 78% with DOR ≥ 6 months, 44% with DOR ≥ 24 months | [8] |
Selpercatinib | 09/21/2022 | RET fusion-positive solid tumors for adult population | LIBRETTO-001 | 41 | ORR = 44% (95% CI: 28, 60), mDOR = 24.5 months (95% CI: 9.2, NE), 67% with DOR ≥ 6 months | [9] |
Trastuzumab Deruxtecan | 04/05/2024 | HER2-positive (IHC3+) solid tumors for adult population | 1. DESTINY-PanTumor02 2. DESTINY-Lung01, 3. DESTINY-CRC02 | 192 | 1. ORR = 51.4% (95% CI: 41.7, 61.0), mDOR = 19.4 (1.3 to 27.9+) months 2. ORR = 52.9% (95% CI: 27.8, 77.0), mDOR = 6.9 (4.0 to 11.7+) months 3. ORR = 46.9% (95% CI: 34.3, 59.8), mDOR = 5.5 (1.3+ to 9.7+) months | [10] |
Reprotrectinib | 06/13/2024 | NTRK gene fusion-positive solid tumors for adult and pediatric patients 12 years or older | TRIDENT-1 | 88 | TKI naïve: ORR = 58% (95% CI: 41,73), mDOR = not estimable (NE) TKI-pretreated: 50% (95% CI: 35,65), mDOR = 9.9 (7.3, 13.0) months | [11] |
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Nguyen, K.; Fama, K.; Mercado, G.; Myat, Y.; Thein, K. Histology Agnostic Drug Development: An Updated Review. Cancers 2024, 16, 3642. https://doi.org/10.3390/cancers16213642
Nguyen K, Fama K, Mercado G, Myat Y, Thein K. Histology Agnostic Drug Development: An Updated Review. Cancers. 2024; 16(21):3642. https://doi.org/10.3390/cancers16213642
Chicago/Turabian StyleNguyen, Kevin, Karina Fama, Guadalupe Mercado, Yin Myat, and Kyaw Thein. 2024. "Histology Agnostic Drug Development: An Updated Review" Cancers 16, no. 21: 3642. https://doi.org/10.3390/cancers16213642
APA StyleNguyen, K., Fama, K., Mercado, G., Myat, Y., & Thein, K. (2024). Histology Agnostic Drug Development: An Updated Review. Cancers, 16(21), 3642. https://doi.org/10.3390/cancers16213642