Ipilimumab Combination Dosing: Less is More
Clin Cancer Res. 2021 Aug 2:clincanres.2406.2021. doi: 10.1158/1078-0432.CCR-21-2406. Online ahead of print.ABSTRACTIpilimumab with and without anti-PD1 improved overall survival in melanoma. Despite this, the optimal dose and therapeutic mechanism of ipilimumab in patients remains unclear. KEYNOTE-029 and other studies suggest that low-dose ipilimumab with anti-PD1 maintains efficacy while decreasing toxicity, emphasizing T cell trafficking and re-invigoration as likely mechanisms.PMID:34341015 | DOI:10.1158/1078-0432.CCR-21-2406 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Authors: Max Jameson-Lee Jason J Luke Source Type: research

Selected Articles from This Issue
Clin Cancer Res. 2021 Aug 1;27(15):4131.NO ABSTRACTPMID:34341052 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Source Type: research

Prediction of Immunotherapy Response in Melanoma through Combined Modeling of Neoantigen Burden and Immune-Related Resistance Mechanisms
CONCLUSIONS: NEOPS proved the statistically strongest biomarker compared with all single-gene biomarkers, expression signatures, and TMB biomarkers evaluated in this cohort. Subsequent confirmation of these findings in an independent cohort of patients (n = 110) suggests that NEOPS is a robust, novel biomarker of ICB response in melanoma.PMID:34341053 | DOI:10.1158/1078-0432.CCR-20-4314 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Authors: Charles W Abbott Sean M Boyle Rachel Marty Pyke Lee D McDaniel Eric Levy F ábio C P Navarro Dattatreya Mellacheruvu Simo V Zhang Mengyao Tan Rose Santiago Zeid M Rusan Pamela Milani Gabor Bartha Jason Harris Rena McClory Michael P Snyder Sekwon Jang Rich Source Type: research

Editor's Note: Biologic Effects of Platelet-Derived Growth Factor Receptor α Blockade in Uterine Cancer
Clin Cancer Res. 2021 Aug 1;27(15):4449. doi: 10.1158/1078-0432.CCR-21-2115.NO ABSTRACTPMID:34341054 | DOI:10.1158/1078-0432.CCR-21-2115 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Authors: Ju-Won Roh Jie Huang Wei Hu XiaoYun Yang Nicholas B Jennings Vasudha Sehgal Bo Hwa Sohn Hee Dong Han Sun Joo Lee Duangmani Thanapprapasr Justin Bottsford-Miller Behrouz Zand Heather J Dalton Rebecca A Previs Ashley N Davis Koji Matsuo Ju-Seog Lee Prahlad Source Type: research

Editor's Note: Targeting Src in Mucinous Ovarian Carcinoma
Clin Cancer Res. 2021 Aug 1;27(15):4450. doi: 10.1158/1078-0432.CCR-21-2116.NO ABSTRACTPMID:34341055 | DOI:10.1158/1078-0432.CCR-21-2116 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Authors: Koji Matsuo Masato Nishimura Justin N Bottsford-Miller Jie Huang Kakajan Komurov Guillermo N Armaiz-Pena Mian M K Shahzad Rebecca L Stone Ju Won Roh Angela M Sanguino Chunhua Lu Dwight D Im Neil B Rosenshien Atsuko Sakakibara Tadayoshi Nagano Masato Yamas Source Type: research

Editor's Note: Dopamine Blocks Stress-mediated Ovarian Carcinoma Growth
Clin Cancer Res. 2021 Aug 1;27(15):4451. doi: 10.1158/1078-0432.CCR-21-2117.NO ABSTRACTPMID:34341056 | DOI:10.1158/1078-0432.CCR-21-2117 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Authors: Myrthala Moreno-Smith Chunhua Lu Mian M K Shahzad Guillermo N Armaiz Pena Julie K Allen Rebecca L Stone Lingegowda S Mangala Hee Dong Han Hye Sun Kim Donna Farley Gabriel Lopez Berestein Steve W Cole Susan K Lutgendorf Anil K Sood Source Type: research

Editor's Note: Functional Roles of < em > Src < /em > and < em > Fgr < /em > in Ovarian Carcinoma
Clin Cancer Res. 2021 Aug 1;27(15):4452. doi: 10.1158/1078-0432.CCR-21-2118.NO ABSTRACTPMID:34341057 | DOI:10.1158/1078-0432.CCR-21-2118 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Authors: Hye-Sun Kim Hee Dong Han Guillermo N Armaiz-Pena Rebecca L Stone Eun Ji Nam Jeong-Won Lee Mian M K Shahzad Alpa M Nick Sun Joo Lee Ju-Won Roh Masato Nishimura Lingegowda S Mangala Justin Bottsford-Miller Gary E Gallick Gabriel Lopez-Berestein Anil K Sood Source Type: research

Editor's Note: Targeted Gene Silencing Using RGD-Labeled Chitosan Nanoparticles
Clin Cancer Res. 2021 Aug 1;27(15):4453. doi: 10.1158/1078-0432.CCR-21-2119.NO ABSTRACTPMID:34341058 | DOI:10.1158/1078-0432.CCR-21-2119 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Authors: Hee Dong Han Lingegowda S Mangala Jeong Won Lee Mian M K Shahzad Hye Sun Kim Deyu Shen Eun Ji Nam Edna M Mora Rebecca L Stone Chunhua Lu Sun Joo Lee Ju Won Roh Alpa M Nick Gabriel Lopez-Berestein Anil K Sood Source Type: research

Editor's Note: Therapeutic Targeting of ATP7B in Ovarian Carcinoma
Clin Cancer Res. 2021 Aug 1;27(15):4454. doi: 10.1158/1078-0432.CCR-21-2120.NO ABSTRACTPMID:34341059 | DOI:10.1158/1078-0432.CCR-21-2120 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Authors: Lingegowda S Mangala Vesna Zuzel Rosemarie Schmandt Erik S Leshane Jyotsna B Halder Guillermo N Armaiz-Pena Whitney A Spannuth Takemi Tanaka Mian M K Shahzad Yvonne G Lin Alpa M Nick Christopher G Danes Jeong-Won Lee Nicholas B Jennings Pablo E Vivas-Meji Source Type: research

Editor's Note: The Clinical Relevance of Stromal Matrix Metalloproteinase Expression in Ovarian Cancer
Clin Cancer Res. 2021 Aug 1;27(15):4455. doi: 10.1158/1078-0432.CCR-21-2121.NO ABSTRACTPMID:34341060 | DOI:10.1158/1078-0432.CCR-21-2121 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Authors: Aparna A Kamat Mavis Fletcher Lynn M Gruman Peter Mueller Adriana Lopez Charles N Landen Liz Han David M Gershenson Anil K Sood Source Type: research

Editor's Note: The Paradoxical Expression of < em > Maspin < /em > in Ovarian Carcinoma
Clin Cancer Res. 2021 Aug 1;27(15):4456. doi: 10.1158/1078-0432.CCR-21-2122.NO ABSTRACTPMID:34341061 | DOI:10.1158/1078-0432.CCR-21-2122 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 3, 2021 Category: Cancer & Oncology Authors: Anil K Sood Mavis S Fletcher Lynn M Gruman Jeremy E Coffin Sarvenaz Jabbari Zhila Khalkhali-Ellis Nancy Arbour Elisabeth A Seftor Mary J C Hendrix Source Type: research

Results and molecular correlates from a pilot study of neoadjuvant induction FOLFIRINOX followed by chemoradiation and surgery for gastroesophageal adenocarcinomas
CONCLUSIONS: Here we show neoadjuvant FOLFIRINOX followed by CRT for locally advanced GEA is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence.PMID:34330715 | DOI:10.1158/1078-0432.CCR-21-0331 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 31, 2021 Category: Cancer & Oncology Authors: Jennifer Y Wo Jeffrey W Clark Christine E Eyler Mari Mino-Kenudson Samuel J Klempner Jill N Allen Florence K Keane Aparna R Parikh Eric Roeland Lorraine C Drapek David P Ryan Ryan B Corcoran Emily Van Seventer Isobel J Fetter Heather A Shahzade Melin J Kh Source Type: research

Results and molecular correlates from a pilot study of neoadjuvant induction FOLFIRINOX followed by chemoradiation and surgery for gastroesophageal adenocarcinomas
CONCLUSIONS: Here we show neoadjuvant FOLFIRINOX followed by CRT for locally advanced GEA is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence.PMID:34330715 | DOI:10.1158/1078-0432.CCR-21-0331 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 31, 2021 Category: Cancer & Oncology Authors: Jennifer Y Wo Jeffrey W Clark Christine E Eyler Mari Mino-Kenudson Samuel J Klempner Jill N Allen Florence K Keane Aparna R Parikh Eric Roeland Lorraine C Drapek David P Ryan Ryan B Corcoran Emily Van Seventer Isobel J Fetter Heather A Shahzade Melin J Kh Source Type: research

Results and molecular correlates from a pilot study of neoadjuvant induction FOLFIRINOX followed by chemoradiation and surgery for gastroesophageal adenocarcinomas
CONCLUSIONS: Here we show neoadjuvant FOLFIRINOX followed by CRT for locally advanced GEA is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence.PMID:34330715 | DOI:10.1158/1078-0432.CCR-21-0331 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 31, 2021 Category: Cancer & Oncology Authors: Jennifer Y Wo Jeffrey W Clark Christine E Eyler Mari Mino-Kenudson Samuel J Klempner Jill N Allen Florence K Keane Aparna R Parikh Eric Roeland Lorraine C Drapek David P Ryan Ryan B Corcoran Emily Van Seventer Isobel J Fetter Heather A Shahzade Melin J Kh Source Type: research

GEN-1 in Combination with Neoadjuvant Chemotherapy for Patients with Advanced Epithelial Ovarian Cancer: A Phase I Dose-Escalation Study
CONCLUSIONS: Adding GEN-1 to standard NAC is safe, appears active and impacts the tumor microenvironment.PMID:34326131 | DOI:10.1158/1078-0432.CCR-21-0360 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 30, 2021 Category: Cancer & Oncology Authors: Premal H Thaker William H Bradley Charles A Leath Camille Gunderson Jackson Nicholas Borys Khursheed Anwer Lauren Musso Junko Matsuzaki Wiam Bshara Kunle Odunsi Ronald D Alvarez Source Type: research

A randomized, phase 3 study of lenvatinib in Chinese patients with radioiodine-refractory differentiated thyroid cancer
Clin Cancer Res. 2021 Jul 29:clincanres.0761.2021. doi: 10.1158/1078-0432.CCR-21-0761. Online ahead of print.ABSTRACTPURPOSE: Lenvatinib has shown efficacy in treating radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the multinational phase 3 SELECT study; however, it has not been tested in Chinese patients with RR-DTC.EXPERIMENTAL DESIGN: Chinese patients with confirmed RR-DTC (n=151) were randomly assigned 2:1 to receive lenvatinib 24 mg/day or placebo in 28-day cycles. The primary endpoint was progression-free survival, and key secondary endpoints included objective response rate and safety. Analyses for...
Source: Clinical Cancer Research - July 30, 2021 Category: Cancer & Oncology Authors: Xiangqian Zheng Zhengang Xu Qinghai Ji Minghua Ge Feng Shi Jianwu Qin Feng Wang Guang Chen Yuan Zhang Rui Huang Jian Tan Tao Huang Sijin Li Zhongwei Lv Yansong Lin Zhuming Guo Tomoki Kubota Takuya Suzuki Hiroki Ikezawa Ming Gao Source Type: research

Location of Gastrointestinal Stromal Tumor (GIST) in the Stomach Predicts Tumor Mutation Profile and Drug Sensitivity
Clin Cancer Res. 2021 Jul 29:clincanres.1221.2021. doi: 10.1158/1078-0432.CCR-21-1221. Online ahead of print.ABSTRACTPURPOSE: Gastrointestinal stromal tumor (GIST) commonly arise in different regions of the stomach and are driven by various mutations (most often in KIT, PDGFRA and SDHx). We hypothesized that the anatomic location of gastric GIST is associated with unique genomic profiles and distinct driver mutations.EXPERIMENTAL DESIGN: We compared KIT versus non-KIT status with tumor location within the National Cancer Database (NCDB) for 2,418 patients with primary gastric GIST. Additionally, we compiled an internationa...
Source: Clinical Cancer Research - July 30, 2021 Category: Cancer & Oncology Authors: Ashwyn K Sharma Jorge De la Torre Nikki S IJzerman Thomas L Sutton Beiqun Zhao Tahsin M Khan Sudeep Banerjee Christina Cui Vi Nguyen Maha Alkhuziem Petur Snaebjornsson Hester Van Boven Annemarie Bruining Chih-Min Tang Hyunho Yoon Alexa De la Fuente Shumei Source Type: research

GEN-1 in Combination with Neoadjuvant Chemotherapy for Patients with Advanced Epithelial Ovarian Cancer: A Phase I Dose-Escalation Study
CONCLUSIONS: Adding GEN-1 to standard NAC is safe, appears active and impacts the tumor microenvironment.PMID:34326131 | DOI:10.1158/1078-0432.CCR-21-0360 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 30, 2021 Category: Cancer & Oncology Authors: Premal H Thaker William H Bradley Charles A Leath Camille Gunderson Jackson Nicholas Borys Khursheed Anwer Lauren Musso Junko Matsuzaki Wiam Bshara Kunle Odunsi Ronald D Alvarez Source Type: research

A randomized, phase 3 study of lenvatinib in Chinese patients with radioiodine-refractory differentiated thyroid cancer
Clin Cancer Res. 2021 Jul 29:clincanres.0761.2021. doi: 10.1158/1078-0432.CCR-21-0761. Online ahead of print.ABSTRACTPURPOSE: Lenvatinib has shown efficacy in treating radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the multinational phase 3 SELECT study; however, it has not been tested in Chinese patients with RR-DTC.EXPERIMENTAL DESIGN: Chinese patients with confirmed RR-DTC (n=151) were randomly assigned 2:1 to receive lenvatinib 24 mg/day or placebo in 28-day cycles. The primary endpoint was progression-free survival, and key secondary endpoints included objective response rate and safety. Analyses for...
Source: Clinical Cancer Research - July 30, 2021 Category: Cancer & Oncology Authors: Xiangqian Zheng Zhengang Xu Qinghai Ji Minghua Ge Feng Shi Jianwu Qin Feng Wang Guang Chen Yuan Zhang Rui Huang Jian Tan Tao Huang Sijin Li Zhongwei Lv Yansong Lin Zhuming Guo Tomoki Kubota Takuya Suzuki Hiroki Ikezawa Ming Gao Source Type: research

Location of Gastrointestinal Stromal Tumor (GIST) in the Stomach Predicts Tumor Mutation Profile and Drug Sensitivity
Clin Cancer Res. 2021 Jul 29:clincanres.1221.2021. doi: 10.1158/1078-0432.CCR-21-1221. Online ahead of print.ABSTRACTPURPOSE: Gastrointestinal stromal tumor (GIST) commonly arise in different regions of the stomach and are driven by various mutations (most often in KIT, PDGFRA and SDHx). We hypothesized that the anatomic location of gastric GIST is associated with unique genomic profiles and distinct driver mutations.EXPERIMENTAL DESIGN: We compared KIT versus non-KIT status with tumor location within the National Cancer Database (NCDB) for 2,418 patients with primary gastric GIST. Additionally, we compiled an internationa...
Source: Clinical Cancer Research - July 30, 2021 Category: Cancer & Oncology Authors: Ashwyn K Sharma Jorge De la Torre Nikki S IJzerman Thomas L Sutton Beiqun Zhao Tahsin M Khan Sudeep Banerjee Christina Cui Vi Nguyen Maha Alkhuziem Petur Snaebjornsson Hester Van Boven Annemarie Bruining Chih-Min Tang Hyunho Yoon Alexa De la Fuente Shumei Source Type: research

Copy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III clinical trial
CONCLUSIONS: Our analysis identified ERBB2 copy number as well as 6q23-24 CNAs as predictors of response to anti-HER2-based treatment. ERBB2 expression outperformed ERBB2 amplification. The complexity of the 6q23-24 region warrants further investigation.PMID:34321278 | DOI:10.1158/1078-0432.CCR-21-1317 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 29, 2021 Category: Cancer & Oncology Authors: David Venet Mattia Rediti Marion Maetens Debora Fumagalli David N Brown Samira Majjaj Roberto Salgado Lajos Pusztai Nadia Harbeck Sarra El-Abed Yingbo Wang Cristina Saura Henry Gomez Vladimir Semiglazov Evandro de Azambuja Jens Huober Paolo Nuciforo Seren Source Type: research

Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration
Clin Cancer Res. 2021 Jul 28:clincanres.1059.2021. doi: 10.1158/1078-0432.CCR-21-1059. Online ahead of print.ABSTRACTThe development of novel agents has transformed the treatment paradigm for multiple myeloma (MM), with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow-based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in MM patients. Complementary liquid biopsy-based assays are now quickly progressing with some, such a...
Source: Clinical Cancer Research - July 29, 2021 Category: Cancer & Oncology Authors: Kenneth C Anderson Daniel Auclair Stacey J Adam Amit Agarwal Melissa Anderson Herve Avet-Loiseau Mark Bustoros Jessica Chapman Dana E Connors Ajeeta Dash Alessandra Di Bacco Ling Du Thierry Facon Juan Flores-Montero Francesca Gay Irene M Ghobrial Nicole J Source Type: research

Phase 1 study of combination pexidartinib and sirolimus to target tumor associated macrophages in unresectable sarcoma and malignant peripheral nerve sheath tumors
CONCLUSIONS: Pexidartinib can be safely administered with sirolimus. These findings support further investigation of this combination to determine clinical efficacy. Clinicaltrials.gov identifier NCT02584647.PMID:34321280 | DOI:10.1158/1078-0432.CCR-21-1779 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 29, 2021 Category: Cancer & Oncology Authors: Gulam A Manji Brian A Van Tine Shing M Lee Alexander Raufi Ilenia Pellicciotta Angela C Hirbe Jaya Pradhan Andrew Chen Raul Rabadan Gary K Schwartz Source Type: research

Copy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III clinical trial
CONCLUSIONS: Our analysis identified ERBB2 copy number as well as 6q23-24 CNAs as predictors of response to anti-HER2-based treatment. ERBB2 expression outperformed ERBB2 amplification. The complexity of the 6q23-24 region warrants further investigation.PMID:34321278 | DOI:10.1158/1078-0432.CCR-21-1317 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 29, 2021 Category: Cancer & Oncology Authors: David Venet Mattia Rediti Marion Maetens Debora Fumagalli David N Brown Samira Majjaj Roberto Salgado Lajos Pusztai Nadia Harbeck Sarra El-Abed Yingbo Wang Cristina Saura Henry Gomez Vladimir Semiglazov Evandro de Azambuja Jens Huober Paolo Nuciforo Seren Source Type: research

Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration
Clin Cancer Res. 2021 Jul 28:clincanres.1059.2021. doi: 10.1158/1078-0432.CCR-21-1059. Online ahead of print.ABSTRACTThe development of novel agents has transformed the treatment paradigm for multiple myeloma (MM), with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow-based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in MM patients. Complementary liquid biopsy-based assays are now quickly progressing with some, such a...
Source: Clinical Cancer Research - July 29, 2021 Category: Cancer & Oncology Authors: Kenneth C Anderson Daniel Auclair Stacey J Adam Amit Agarwal Melissa Anderson Herve Avet-Loiseau Mark Bustoros Jessica Chapman Dana E Connors Ajeeta Dash Alessandra Di Bacco Ling Du Thierry Facon Juan Flores-Montero Francesca Gay Irene M Ghobrial Nicole J Source Type: research

Phase 1 study of combination pexidartinib and sirolimus to target tumor associated macrophages in unresectable sarcoma and malignant peripheral nerve sheath tumors
CONCLUSIONS: Pexidartinib can be safely administered with sirolimus. These findings support further investigation of this combination to determine clinical efficacy. Clinicaltrials.gov identifier NCT02584647.PMID:34321280 | DOI:10.1158/1078-0432.CCR-21-1779 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 29, 2021 Category: Cancer & Oncology Authors: Gulam A Manji Brian A Van Tine Shing M Lee Alexander Raufi Ilenia Pellicciotta Angela C Hirbe Jaya Pradhan Andrew Chen Raul Rabadan Gary K Schwartz Source Type: research

Perspectives on Drug Development in Multiple Myeloma-Looking forward to 2025
This article summarizes the highlights of this educational symposium held at the FDA, including discussions on the future development of novel drugs and drug combinations and biomarker-directed therapies for patients with MM.PMID:34315721 | DOI:10.1158/1078-0432.CCR-21-1069 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 28, 2021 Category: Cancer & Oncology Authors: Peter M Voorhees Andrzej J Jakubowiak Shaji K Kumar Bindu Kanapuru Andrea C Baines Vishal Bhatnagar Rachel Ershler Marc R Theoret Nicole J Gormley Richard Pazdur Source Type: research

Randomized phase II study of axitinib versus observation in patients with recurred or metastatic adenoid cystic carcinoma
Clin Cancer Res. 2021 Jul 27:clincanres.1061.2021. doi: 10.1158/1078-0432.CCR-21-1061. Online ahead of print.ABSTRACTPURPOSE: The role of chemotherapy in adenoid cystic carcinoma (ACC) is controversial because ACC is usually stable without chemotherapy and lack of randomized trials. Here, we conducted the first randomized trial to evaluate the efficacy of axitinib as compared to observation in ACC.PATIENTS AND METHODS: In this multicenter, prospective phase II trial, we enrolled patients with recurrent or metastatic ACC whose cancer had progressed within the past 9 months. Patients were randomly assigned to either axitinib...
Source: Clinical Cancer Research - July 28, 2021 Category: Cancer & Oncology Authors: Eun Joo Kang Myung-Ju Ahn Chan-Young Ock Keun-Wook Lee Jung Hye Kwon Yaewon Yang Yoon Hee Choi Min Kyoung Kim Jun Ho Ji Tak Yun Byung-Ho Nam Sung-Bae Kim Bhumsuk Keam Source Type: research

Tumor-specific major histocompatibility-II expression predicts benefit to anti-PD-1/L1 therapy in patients with HER2-negative primary breast cancer
CONCLUSIONS: Tumor-specific MHC-II has strong candidacy as a specific biomarker of anti-PD-1/L1 immunotherapy benefit when added to standard NAC in HER2-negative breast cancer. Combined with previous studies in melanoma, MHCII has the potential to be a pan-cancer biomarker. Validation is warranted in existing and future Phase II/III clinical trials in this setting.PMID:34315723 | DOI:10.1158/1078-0432.CCR-21-0607 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 28, 2021 Category: Cancer & Oncology Authors: Paula I Gonzalez-Ericsson Julia D Wulfkhule Rosa I Gallagher Xiaopeng Sun Margaret L Axelrod Quanhu Sheng Na Luo Henry Gomez Violeta Sanchez Melinda Sanders Lajos Pusztai Emanuel F Petricoin Kim Rm Blenman Justin M Balko I-Spy Trial Team Source Type: research

Clinical Trials with Biologic Primary Endpoints in Immuno-oncology: Concepts and Usage
Clin Cancer Res. 2021 Jul 26:clincanres.1593.2021. doi: 10.1158/1078-0432.CCR-21-1593. Online ahead of print.ABSTRACTClinical trials that have a pharmacokinetic or a pharmacodynamic immunologic mechanism of action based primary outcome, could substantially improve the validity and efficiency of early development of immuno-oncology agents. Here, we outline different trial design options in this area, review examples from the literature and their unique immunologic aspects, and highlight how these trials have been underutilized. We illustrate how new technologies and translationally focused approaches can be successfully use...
Source: Clinical Cancer Research - July 27, 2021 Category: Cancer & Oncology Authors: James Isaacs Aaron C Tan Brent A Hanks Xiaofei Wang Kouros Owzar James E Herndon Scott J Antonia Steven Piantadosi Mustafa Khasraw Source Type: research

A grant-based experiment to train clinical investigators: the AACR/ASCO methods in clinical cancer research workshop
Discussion Sessions; (3) Protocol Development Groups; (4) one-on-one mentoring. Learning focused on the development of an IRB-ready protocol, which was submitted on the last day of the workshop. Evaluation methods included: (1) pre- and post-workshop tests; (2) students' workshop evaluations; (3) faculty's ratings of protocol development; (4) students' productivity in clinical research after the workshop; (5) an independent assessment of the workshop. From 1996-2014, 1932 students from diverse backgrounds attended the workshop. There was a significant improvement in the students' level of knowledge from the pre- to the post-workshop exams (p
Source: Clinical Cancer Research - July 27, 2021 Category: Cancer & Oncology Authors: Daniel D Von Hoff Gary M Clark Charles A Coltman Mary L Disis S Gail Eckhardt Lee M Ellis Margaret Foti Elizabeth Garrett-Mayer Mithat Gonen Manuel Hidalgo Susan G Hilsenbeck John H Littlefield Patricia M LoRusso H Kim Lyerly Neal J Meropol Jyoti D Patel Source Type: research

Clinical Trials with Biologic Primary Endpoints in Immuno-oncology: Concepts and Usage
Clin Cancer Res. 2021 Jul 26:clincanres.1593.2021. doi: 10.1158/1078-0432.CCR-21-1593. Online ahead of print.ABSTRACTClinical trials that have a pharmacokinetic or a pharmacodynamic immunologic mechanism of action based primary outcome, could substantially improve the validity and efficiency of early development of immuno-oncology agents. Here, we outline different trial design options in this area, review examples from the literature and their unique immunologic aspects, and highlight how these trials have been underutilized. We illustrate how new technologies and translationally focused approaches can be successfully use...
Source: Clinical Cancer Research - July 27, 2021 Category: Cancer & Oncology Authors: James Isaacs Aaron C Tan Brent A Hanks Xiaofei Wang Kouros Owzar James E Herndon Scott J Antonia Steven Piantadosi Mustafa Khasraw Source Type: research

A grant-based experiment to train clinical investigators: the AACR/ASCO methods in clinical cancer research workshop
Discussion Sessions; (3) Protocol Development Groups; (4) one-on-one mentoring. Learning focused on the development of an IRB-ready protocol, which was submitted on the last day of the workshop. Evaluation methods included: (1) pre- and post-workshop tests; (2) students' workshop evaluations; (3) faculty's ratings of protocol development; (4) students' productivity in clinical research after the workshop; (5) an independent assessment of the workshop. From 1996-2014, 1932 students from diverse backgrounds attended the workshop. There was a significant improvement in the students' level of knowledge from the pre- to the post-workshop exams (p
Source: Clinical Cancer Research - July 27, 2021 Category: Cancer & Oncology Authors: Daniel D Von Hoff Gary M Clark Charles A Coltman Mary L Disis S Gail Eckhardt Lee M Ellis Margaret Foti Elizabeth Garrett-Mayer Mithat Gonen Manuel Hidalgo Susan G Hilsenbeck John H Littlefield Patricia M LoRusso H Kim Lyerly Neal J Meropol Jyoti D Patel Source Type: research

Liquid Biopsy Goes Viral: Next-Generation Sequencing to Enhance HPV Detection
Clin Cancer Res. 2021 Jul 22:clincanres.2180.2021. doi: 10.1158/1078-0432.CCR-21-2180. Online ahead of print.ABSTRACTLiquid biopsy approaches for the detection of viral DNA can provide important information for the diagnosis and identification of virally-associated cancers. Here we discuss the next-generation sequencing (NGS)-based CaptHPV method for the detection and characterization of plasma human papillomavirus (HPV) DNA in HPV-associated cancers and its potential clinical utility.PMID:34301747 | DOI:10.1158/1078-0432.CCR-21-2180 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Ariana Rostami Scott V Bratman Kathy Han Source Type: research

FDA Approval Summary: Osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review
Clin Cancer Res. 2021 Jul 22:clincanres.1034.2021. doi: 10.1158/1078-0432.CCR-21-1034. Online ahead of print.ABSTRACTOn December 18, 2020, the U.S. Food and Drug Administration (FDA) approved osimertinib as adjuvant therapy in patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations, as detected by an FDA-approved test. The approval was based on the ADAURA study in which 682 patients with NSCLC were randomized to receive osimertinib (n=339) or placebo (n=343). Disease free survival (DFS) in the overall population (Stage IB-IIIA...
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Abigail L Koch Paz J Vellanki Nicole Drezner Xiaoxue Li Pallavi S Mishra-Kalyani Yuan Li Shen Huiming Xia Yangbing Li Jiang Liu Jeanne Fourie Zirkelbach Elitza Palazov Aleksandr Gamarian Qiuyi Choo Ar ūnas Girčys Ulrich-Peter Rohr Nataliya Fesenko Diann Source Type: research

Niraparib for advanced breast cancer with germline < em > BRCA1 < /em > and < em > BRCA2 < /em > mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO study
CONCLUSION: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.PMID:34301749 | DOI:10.1158/1078-0432.CCR-21-0310 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Nicholas C Turner Judith Balma ña Coralie Poncet Theodora Goulioti Konstantinos Tryfonidis Aafke H Honkoop Gabriele Zoppoli Evangelia Razis Oskar Th Johannsson Marco Colleoni Andrew N J Tutt William Audeh Michail Ignatiadis Audrey Mailliez Olivier Tr éd Source Type: research

Phase 1 Trial of ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Patients with Solid Tumors and Lymphomas Bearing Wild-Type < em > TP53 < /em >
CONCLUSION: ALRN-6924 was well tolerated and demonstrated anti-tumor activity.PMID:34301750 | DOI:10.1158/1078-0432.CCR-21-0715 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Mansoor N Saleh Manish R Patel Todd M Bauer Sanjay Goel Gerald S Falchook Geoffrey I Shapiro Ki Y Chung Jeffrey R Infante Robert M Conry Guilherme Rabinowits David S Hong Judy S Wang Ulrich Steidl Gurudatta Naik Vincent Guerlavais Vojislav Vukovic D Allen Source Type: research

RELAY Subgroup Analyses by EGFR Ex19del and Ex21L858R Mutations for Ramucirumab Plus Erlotinib in Metastatic Non-small Cell Lung Cancer
CONCLUSIONS: RAM+ERL provided significant clinical benefit for both EGFR ex19del and ex21L858R NSCLC, supporting this regimen as suitable for patients with either of these EGFR mutation types.PMID:34301751 | DOI:10.1158/1078-0432.CCR-21-0273 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Kazuhiko Nakagawa Ernest Nadal Edward B Garon Makoto Nishio Takashi Seto Nobuyuki Yamamoto Keunchil Park Jin-Yuan Shih Luis Paz-Ares Bente Frimodt-Moller Annamaria H Zimmermann Sameera Wijayawardana Carla Visseren-Grul Martin Reck Source Type: research

Ceralasertib (AZD6738), an oral ATR kinase inhibitor, in combination with carboplatin in patients with advanced solid tumors: a Phase I study
CONCLUSIONS: The RP2D for ceralasertib plus carboplatin was established as ceralasertib 40 mg QD on days 1-2 administered with carboplatin AUC5 every 3 weeks, with pharmacokinetic and pharmacodynamic studies confirming pharmacodynamic modulation and preliminary evidence of antitumor activity observed.PMID:34301752 | DOI:10.1158/1078-0432.CCR-21-1032 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Timothy A Yap Matthew G Krebs Sophie Postel-Vinay Anthony El-Khouiery Jean-Charles Soria Juanita Lopez Alienor Berges S Y Amy Cheung Itziar Irurzun-Arana Andrew Goldwin Brunella Felicetti Gemma N Jones Alan Lau Paul Frewer Andrew J Pierce Glen Clack Chris Source Type: research

BCMA-specific ADC MEDI2228 and Daratumumab induce synergistic myeloma cytotoxicity via IFN-driven immune responses and enhanced CD38 expression
CONCLUSIONS: These results provide the basis for clinical evaluation of combination MEDI2228 with Dara to further improve patient outcome in MM.PMID:34301753 | DOI:10.1158/1078-0432.CCR-21-1621 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Lijie Xing Su Wang Jiye Liu Tengteng Yu Hailin Chen Kenneth Wen Yuyin Li Liang Lin Phillip A Hsieh Shih-Feng Cho Gang An Lugui Qiu Krista Kinneer Nikhil Munshi Kenneth C Anderson Yu-Tzu Tai Source Type: research

Liquid Biopsy Goes Viral: Next-Generation Sequencing to Enhance HPV Detection
Clin Cancer Res. 2021 Jul 22:clincanres.2180.2021. doi: 10.1158/1078-0432.CCR-21-2180. Online ahead of print.ABSTRACTLiquid biopsy approaches for the detection of viral DNA can provide important information for the diagnosis and identification of virally-associated cancers. Here we discuss the next-generation sequencing (NGS)-based CaptHPV method for the detection and characterization of plasma human papillomavirus (HPV) DNA in HPV-associated cancers and its potential clinical utility.PMID:34301747 | DOI:10.1158/1078-0432.CCR-21-2180 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Ariana Rostami Scott V Bratman Kathy Han Source Type: research

FDA Approval Summary: Osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review
Clin Cancer Res. 2021 Jul 22:clincanres.1034.2021. doi: 10.1158/1078-0432.CCR-21-1034. Online ahead of print.ABSTRACTOn December 18, 2020, the U.S. Food and Drug Administration (FDA) approved osimertinib as adjuvant therapy in patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations, as detected by an FDA-approved test. The approval was based on the ADAURA study in which 682 patients with NSCLC were randomized to receive osimertinib (n=339) or placebo (n=343). Disease free survival (DFS) in the overall population (Stage IB-IIIA...
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Abigail L Koch Paz J Vellanki Nicole Drezner Xiaoxue Li Pallavi S Mishra-Kalyani Yuan Li Shen Huiming Xia Yangbing Li Jiang Liu Jeanne Fourie Zirkelbach Elitza Palazov Aleksandr Gamarian Qiuyi Choo Ar ūnas Girčys Ulrich-Peter Rohr Nataliya Fesenko Diann Source Type: research

Niraparib for advanced breast cancer with germline < em > BRCA1 < /em > and < em > BRCA2 < /em > mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO study
CONCLUSION: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.PMID:34301749 | DOI:10.1158/1078-0432.CCR-21-0310 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Nicholas C Turner Judith Balma ña Coralie Poncet Theodora Goulioti Konstantinos Tryfonidis Aafke H Honkoop Gabriele Zoppoli Evangelia Razis Oskar Th Johannsson Marco Colleoni Andrew N J Tutt William Audeh Michail Ignatiadis Audrey Mailliez Olivier Tr éd Source Type: research

Phase 1 Trial of ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Patients with Solid Tumors and Lymphomas Bearing Wild-Type < em > TP53 < /em >
CONCLUSION: ALRN-6924 was well tolerated and demonstrated anti-tumor activity.PMID:34301750 | DOI:10.1158/1078-0432.CCR-21-0715 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Mansoor N Saleh Manish R Patel Todd M Bauer Sanjay Goel Gerald S Falchook Geoffrey I Shapiro Ki Y Chung Jeffrey R Infante Robert M Conry Guilherme Rabinowits David S Hong Judy S Wang Ulrich Steidl Gurudatta Naik Vincent Guerlavais Vojislav Vukovic D Allen Source Type: research

RELAY Subgroup Analyses by EGFR Ex19del and Ex21L858R Mutations for Ramucirumab Plus Erlotinib in Metastatic Non-small Cell Lung Cancer
CONCLUSIONS: RAM+ERL provided significant clinical benefit for both EGFR ex19del and ex21L858R NSCLC, supporting this regimen as suitable for patients with either of these EGFR mutation types.PMID:34301751 | DOI:10.1158/1078-0432.CCR-21-0273 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Kazuhiko Nakagawa Ernest Nadal Edward B Garon Makoto Nishio Takashi Seto Nobuyuki Yamamoto Keunchil Park Jin-Yuan Shih Luis Paz-Ares Bente Frimodt-Moller Annamaria H Zimmermann Sameera Wijayawardana Carla Visseren-Grul Martin Reck Source Type: research

Ceralasertib (AZD6738), an oral ATR kinase inhibitor, in combination with carboplatin in patients with advanced solid tumors: a Phase I study
CONCLUSIONS: The RP2D for ceralasertib plus carboplatin was established as ceralasertib 40 mg QD on days 1-2 administered with carboplatin AUC5 every 3 weeks, with pharmacokinetic and pharmacodynamic studies confirming pharmacodynamic modulation and preliminary evidence of antitumor activity observed.PMID:34301752 | DOI:10.1158/1078-0432.CCR-21-1032 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Timothy A Yap Matthew G Krebs Sophie Postel-Vinay Anthony El-Khouiery Jean-Charles Soria Juanita Lopez Alienor Berges S Y Amy Cheung Itziar Irurzun-Arana Andrew Goldwin Brunella Felicetti Gemma N Jones Alan Lau Paul Frewer Andrew J Pierce Glen Clack Chris Source Type: research

BCMA-specific ADC MEDI2228 and Daratumumab induce synergistic myeloma cytotoxicity via IFN-driven immune responses and enhanced CD38 expression
CONCLUSIONS: These results provide the basis for clinical evaluation of combination MEDI2228 with Dara to further improve patient outcome in MM.PMID:34301753 | DOI:10.1158/1078-0432.CCR-21-1621 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Lijie Xing Su Wang Jiye Liu Tengteng Yu Hailin Chen Kenneth Wen Yuyin Li Liang Lin Phillip A Hsieh Shih-Feng Cho Gang An Lugui Qiu Krista Kinneer Nikhil Munshi Kenneth C Anderson Yu-Tzu Tai Source Type: research

Liquid Biopsy Goes Viral: Next-Generation Sequencing to Enhance HPV Detection
Clin Cancer Res. 2021 Jul 22:clincanres.2180.2021. doi: 10.1158/1078-0432.CCR-21-2180. Online ahead of print.ABSTRACTLiquid biopsy approaches for the detection of viral DNA can provide important information for the diagnosis and identification of virally-associated cancers. Here we discuss the next-generation sequencing (NGS)-based CaptHPV method for the detection and characterization of plasma human papillomavirus (HPV) DNA in HPV-associated cancers and its potential clinical utility.PMID:34301747 | DOI:10.1158/1078-0432.CCR-21-2180 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Ariana Rostami Scott V Bratman Kathy Han Source Type: research

FDA Approval Summary: Osimertinib for adjuvant treatment of surgically resected non-small cell lung cancer, a collaborative Project Orbis review
Clin Cancer Res. 2021 Jul 22:clincanres.1034.2021. doi: 10.1158/1078-0432.CCR-21-1034. Online ahead of print.ABSTRACTOn December 18, 2020, the U.S. Food and Drug Administration (FDA) approved osimertinib as adjuvant therapy in patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations, as detected by an FDA-approved test. The approval was based on the ADAURA study in which 682 patients with NSCLC were randomized to receive osimertinib (n=339) or placebo (n=343). Disease free survival (DFS) in the overall population (Stage IB-IIIA...
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Abigail L Koch Paz J Vellanki Nicole Drezner Xiaoxue Li Pallavi S Mishra-Kalyani Yuan Li Shen Huiming Xia Yangbing Li Jiang Liu Jeanne Fourie Zirkelbach Elitza Palazov Aleksandr Gamarian Qiuyi Choo Ar ūnas Girčys Ulrich-Peter Rohr Nataliya Fesenko Diann Source Type: research

Niraparib for advanced breast cancer with germline < em > BRCA1 < /em > and < em > BRCA2 < /em > mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO study
CONCLUSION: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.PMID:34301749 | DOI:10.1158/1078-0432.CCR-21-0310 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - July 24, 2021 Category: Cancer & Oncology Authors: Nicholas C Turner Judith Balma ña Coralie Poncet Theodora Goulioti Konstantinos Tryfonidis Aafke H Honkoop Gabriele Zoppoli Evangelia Razis Oskar Th Johannsson Marco Colleoni Andrew N J Tutt William Audeh Michail Ignatiadis Audrey Mailliez Olivier Tr éd Source Type: research