PMID- 37561967 OWN - NLM STAT- MEDLINE DCOM- 20231117 LR - 20231117 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 41 IP - 33 DP - 2023 Nov 20 TI - Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study. PG - 5140-5150 LID - 10.1200/JCO.23.00702 [doi] AB - PURPOSE: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a pragmatic basket trial evaluating antitumor activity of approved targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from cohorts of patients with high tumor mutational burden (HTMB, defined as >/=9 mutations per megabase) with advanced colorectal cancer (CRC) and other advanced cancers treated with pembrolizumab are reported. METHODS: Eligible patients were 18 years and older with measurable tumors and a lack of standard treatment options, an Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. The primary end point was disease control (DC), defined as complete or partial response or stable disease (SD) of at least 16-weeks duration. For the CRC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; alpha = .10) was used. Low accruing histology-specific cohorts were collapsed into one histology-pooled (HP) cohort. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included objective response (OR), safety, progression-free survival, overall survival, duration of response, and duration of SD. RESULTS: Seventy-seven patients with HTMB with CRC (n = 28) or advanced cancers (n = 49) were treated with pembrolizumab. For the CRC cohort, the DC rate was 31% (P = .04) and the OR rate was 11%. For the HP cohort, the DC rate was 45% (one-sided 90% CI, 35 to 100) and the OR rate was 26%. The null hypothesis of a 15% DC rate was rejected for both cohorts. Twelve of 77 patients experienced treatment-related grade 3 adverse events (AEs) or serious AEs, including two deaths. CONCLUSION: Pembrolizumab demonstrated antitumor activity in pretreated patients with advanced cancers and HTMB. FAU - Duvivier, Herbert L AU - Duvivier HL AD - Cancer Treatment Centers of America-Atlanta, Part of City of Hope, Newnan, GA. FAU - Rothe, Michael AU - Rothe M AD - American Society of Clinical Oncology, Alexandria, VA. FAU - Mangat, Pam K AU - Mangat PK AUID- ORCID: 0000-0001-8571-6742 AD - American Society of Clinical Oncology, Alexandria, VA. FAU - Garrett-Mayer, Elizabeth AU - Garrett-Mayer E AUID- ORCID: 0000-0003-4709-0333 AD - American Society of Clinical Oncology, Alexandria, VA. FAU - Ahn, Eugene R AU - Ahn ER AD - Cancer Treatment Centers of America-Chicago, Part of City of Hope, Zion, IL. FAU - Al Baghdadi, Tareq AU - Al Baghdadi T AD - Michigan Cancer Research Consortium, IHA Hematology Oncology, Ypsilanti, MI. FAU - Alva, Ajjai S AU - Alva AS AD - University of Michigan Rogel Comprehensive Cancer Center, Ann Arbor, MI. FAU - Dublis, Stephanie A AU - Dublis SA AD - University of Michigan Health-West, Wyoming, MI. FAU - Cannon, Timothy L AU - Cannon TL AUID- ORCID: 0000-0001-5033-3071 AD - Inova Schar Cancer Institute, Fairfax, VA. FAU - Calfa, Carmen J AU - Calfa CJ AUID- ORCID: 0000-0003-2824-0930 AD - Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL. FAU - Li, Rui AU - Li R AD - Providence Cancer Institute, Providence Portland Medical Center, Portland, OR. FAU - Behl, Deepti AU - Behl D AUID- ORCID: 0000-0002-8247-5055 AD - Sutter Sacramento Medical Center, Sacramento, CA. FAU - Chiu, Vi K AU - Chiu VK AD - The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Los Angeles, CA. FAU - Gold, Philip J AU - Gold PJ AD - Swedish Cancer Institute, Seattle, WA. FAU - Marr, Alissa S AU - Marr AS AUID- ORCID: 0000-0002-2545-3570 AD - University of Nebraska Medical Center, Omaha, NE. FAU - Mileham, Kathryn F AU - Mileham KF AUID- ORCID: 0000-0003-1334-7743 AD - Levine Cancer Institute, Atrium Health, Charlotte, NC. FAU - Powell, Steven Francis AU - Powell SF AUID- ORCID: 0000-0002-5029-0048 AD - Sanford Health, Sioux Falls, SD. FAU - Rodon, Jordi AU - Rodon J AUID- ORCID: 0000-0001-6467-3632 AD - Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Thota, Ramya AU - Thota R AUID- ORCID: 0000-0001-6538-9924 AD - Intermountain Healthcare, Murray, UT. FAU - Grantham, Gina N AU - Grantham GN AUID- ORCID: 0000-0002-3111-0419 AD - American Society of Clinical Oncology, Alexandria, VA. FAU - Gregory, Abigail AU - Gregory A AUID- ORCID: 0000-0001-9189-4369 AD - American Society of Clinical Oncology, Alexandria, VA. FAU - Hinshaw, Dominique C AU - Hinshaw DC AUID- ORCID: 0000-0002-2052-9484 AD - American Society of Clinical Oncology, Alexandria, VA. FAU - Halabi, Susan AU - Halabi S AUID- ORCID: 0000-0003-4135-2777 AD - Duke University Medical Center, Durham, NC. FAU - Schilsky, Richard L AU - Schilsky RL AUID- ORCID: 0000-0003-4474-4303 AD - American Society of Clinical Oncology, Alexandria, VA. LA - eng SI - ClinicalTrials.gov/NCT02693535 PT - Journal Article DEP - 20230810 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - DPT0O3T46P (pembrolizumab) RN - 0 (Antineoplastic Agents) RN - 0 (Antibodies, Monoclonal, Humanized) SB - IM MH - Humans MH - *Antineoplastic Agents/therapeutic use MH - Antibodies, Monoclonal, Humanized/adverse effects MH - *Colorectal Neoplasms/drug therapy/genetics EDAT- 2023/08/10 18:41 MHDA- 2023/11/17 15:23 CRDT- 2023/08/10 16:03 PHST- 2023/11/17 15:23 [medline] PHST- 2023/08/10 18:41 [pubmed] PHST- 2023/08/10 16:03 [entrez] AID - 10.1200/JCO.23.00702 [doi] PST - ppublish SO - J Clin Oncol. 2023 Nov 20;41(33):5140-5150. doi: 10.1200/JCO.23.00702. Epub 2023 Aug 10.