DOI: 10.1200/oa-26-00057 ISSN: 2994-9750

Favezelimab/Pembrolizumab Coformulation Versus Standard-of-Care in PD-L1–Positive Metastatic Colorectal Cancer: The Phase III, Randomized KEYFORM-007 Study

Neil Howard Segal, Maria Passhak, Fatih Köse, Elena Elez, Hisato Kawakami, Marianne G. Guren, Derek Jonker, Rui-Hua Xu, Jorge Riera Knorrenschild, Yu-Min Yeh, Mastura Yusof, Kai Keen Shiu, Naureen Starling, Xiang Peng, David R. Fogelman, David Adelberg, Tae Won Kim, , Timothy Price, Timothy Dudley Clay, Peter Gibbs, Babak Tamjid, Adnan Nagrial, Matthew Burke, Derek James Jonker, John Gordon Lenehan, Xueyu Eric Chen, Jaime Gonzalez, Luisa Elena Morales, Patrocio Eduardo Yanez Weber, Anrried Escalante, Bruno Nervi, Felipe Reyes, Rodrigo Vasquez, Claudio Painemal, Ruihua Xu, Yongsheng Li, Shaozhong Wei, Wangjun Liao, Yuxian Bai, Yongqiang Li, Yanhong Deng, Yi Ba, Tao Zhang, Ying Cheng, Xianbao Zhan, Meili Sun, Yunfeng Li, Qing Xu, Heli Liu, Meng Qiu, Hongming Pan, Xianli Yin, Qi Wang, Zhiyu Chem, Xue Hua Xing, Yigui Chen, Mingjun Zhang, Wang Xia LV, Qi Li, Jianzhong Xu, Yong Mao, Jana Prausova, Petra Beran Holeckova, Igor Kiss, Bohuslav Melichar, Eugen Kubala, Stanislav John, Marian Liberko, Yann Toucehfeu, David Tougeron, Denis Smith, Laurent Mineur, Claire Gallois, Petra Buechner-Steudel, Jorge Riera Knorrenschild, Volker Heinemann, Yon-Dschun Ko, Ullrich Graeven, Nils Homann, Gunnar Hapke, Maria Passhak, Einat Shacham-Shmueli, Ravit Geva, Ayala Hubert, Rasha Khoury, Ofer Purim, Gali Perl, Salvatore Siena, Giampaolo Tortora, Roberto Bordonaro, Evaristo Maiello, Armando Santoro, Fortunato Ciardiello, Daisuke Kotani, Atsuo Takashima, Kensei Yamaguchi, Hiroki Hara, Kentaro Yamazaki, Chiaki Inagaki, Akihito Tsuji, Taito Esaki, Wan Zamaniah Wan Ishak, Suhana Binti Yusak, Mastura Md Yusof, Mohamed Ibrahim Abdul Wahid, Marianne Grønlie Guren, Christina Tanem Møller, Kristine Aasebo, Eva Hofsli, Helge Stenvold, Sze Wai Chan, John Malcom Crockett, Conrad Rudolph Jacobs, Jean-Marc Joseph Maurel, Tae Won Kim, Seung Bae Kim, Joong Bae Ahn, Tae-You Kim, Nikolay Viktorovich Kislov, Anna Kedrova, Madina Sultanovna Ramazanova, Nikita Mikhaylovich Volkov, Alexey Vladimirovich Smolin, Alsu Inzerovna Iskhakova, Stanislav Patalyak, Andrey Lebedinets, Dimitri Gladyshev, Elena Elez Fernandez, Rocio Garcia Carbonero, Javier Sastre Valera, David Paez Lopez-Bravo, Juan Jose Raina Zoilo, Kun-Huei Yeh, Hao-Wei Teng, Hung-Chih Hsu, Hwei-Ming Wang, Yu-Min Yeh, Hong-Hwa Chen, Mahmut Gumus, Suayib Yalcin, Dogan Uncu, Pinar Gursoy, Fatih Kose, Umut Disel, Nuri Karadurmus, Mustafa Karaca, Jenny Seligmann, Harpreet Wasan, Kai-Keen Shiu, Sonali Dasgupta, Vanessa Potter, Naureen Starling, Anna Kryzhanivska, Igor Bondarenko, Stepan Krulko, Yurii Osypchuk, Patrick McKay Boland, Elena Gabriela Chiorean, Steven McCune, Raymond C. Wadlow, Michael Driscoll, Adel Kardosh, Michael Jon Pishvaian, Benjamin Weinberg, Bradley G. Somer, Neil Segal, Ramya Thota, Syed Mohammad Ali Kazmi, Jennifer Myers, Paul O'Brien, Mark D. Kochenderfer
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Purpose

The phase III KEYFORM-007 study (ClinicalTrials.gov identifier: NCT05064059 ) evaluated the efficacy and safety of coformulated favezelimab/pembrolizumab versus standard-of-care (SOC) in PD-L1–positive microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC). We present results of the final analysis of overall survival (OS).

Methods

Eligible participants with PD-L1 combined positive score ≥1, MSS/pMMR unresectable mCRC who had progressed on or could not tolerate standard treatment were randomly assigned 1:1 to coformulated favezelimab 800 mg/pembrolizumab 200 mg intravenously once every 3 weeks or SOC (regorafenib 160 mg orally once every 4 weeks [once daily on days 1-21] or TAS-102 35 mg/m 2 orally once every 4 weeks [twice a day on days 1-5 and 8-12]). The primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety.

Results

At final analysis, 441 participants were randomly assigned (221 favezelimab/pembrolizumab; 220 SOC). Median follow-up was 28 months (range, 21-32). OS was not superior with favezelimab/pembrolizumab versus SOC (median 7.3 v 8.5 months; hazard ratio [HR], 0.98 [95% CI, 0.80 to 1.20]; P = .4183) in participants with MSS/pMMR mCRC. PFS was not superior with favezelimab/pembrolizumab versus SOC (median 2.1 v 2.6 months; HR, 1.34 [95% CI, 1.09 to 1.64]; nominal P = .997). The ORR was 6.8% (14 partial response [PR]; one complete response) versus 0.9% (two PR) with favezelimab/pembrolizumab versus SOC. Median DOR was not reached (range, 1.8 to 16.8+) among the 15 responders in the favezelimab/pembrolizumab arm and was 6.5+ months and 12.4 months for the two responders in the SOC arm. Grade ≥3 treatment-related adverse events occurred in 44 (20%) and 76 (36%) participants, respectively.

Conclusion

At final analysis, coformulated favezelimab/pembrolizumab did not improve OS versus SOC in patients with PD-L1–positive MSS/pMMR mCRC. The safety profile was manageable with no new safety signals observed. This coformulation is not recommended for use in this patient population.

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