PD-L1 CDx Earns FDA Approval to Identify PD-L1+ Gastric/GEJ Tumors

News
Article

Approval of PD-L1 IHC 22C3 pharmDx may also identify patients with non–small cell lung cancer and other malignancies who may benefit from treatment with pembrolizumab.

The FDA originally approved pembrolizumab plus trastuzumab and chemotherapy for patients with advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in May 2021.

The FDA originally approved pembrolizumab plus trastuzumab and chemotherapy for patients with advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in May 2021.

The FDA has granted approval to PD-L1 IHC 22C3 pharmDx as a companion diagnostic to determine which patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma are eligibile for recipt of pembrolizumab (Keytruda), according to a press release from Agilent.1

According to the press release, PD-L1 IHC 22C3 pharmDx is the only companion diagnostic to receive FDA approval for identifying patients with gastric or GEJ adenocarcinoma who may benefit from select treatments such as pembrolizumab, chemotherapy, trastuzumab (Herceptin), and fluoropyrimidine. Additionally, it is believed that the companion diagnostic may help spotlight those with non–small cell lung cancer, esophageal squamous cell carcinoma, cervical cancer, head and neck squamous cell carcinoma, and triple-negative breast cancer who could be eligible for treatment with pembrolizumab.

“PD-L1 expression is a critical biomarker for response to anti–PD-1 therapies such as [pembrolizumab],” Lou Welebob, vice president and general manager of Agilent’s Pathology Division, said in the press release.1 “This endorsement underscores Agilent’s leadership in the development of companion diagnostics for groundbreaking anti-PD-1 therapies.”

The FDA originally approved pembrolizumab plus trastuzumab and chemotherapy for patients with advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in May 2021.2 The regimen was granted accelerated approval status based on data from the phase 3 KEYNOTE-811 trial (NCT03615326).

Findings published at the time of the approval highlighted an objective response rate (ORR) of 74% (95% CI, 66%-82%) with pembrolizumab plus chemotherapy vs 52% (95% CI, 43%-61%) with chemotherapy alone. The median duration of response (DOR) in the experimental and control arms, respectively, was 10.6 months (range, 1.1+ to 16.5+) vs 9.5 months (range, 1.4+ to 15.4+).

The FDA updated the indication for frontline pembrolizumab in HER2-positive gastric or GEJ adenocarcinoma in November 2023.3 Only patients with a PD-L1 combined positive score (CPS) of 1 or higher as confirmed by an FDA-approved test were able to receive pembrolizumab in combination with trastuzumab and chemotherapy following the indication’s revision. The regulatory agency made no changes to the regimen’s accelerated approval status.

In the KEYNOTE-811 trial, patients were randomly assigned to receive 200 mg of pembrolizumab intravenously or matched placebo on day 1 of each 3-week cycle. All patients also received trastuzumab at 8 mg/kg as a loading dose and at 6 mg/kg as maintenance thereafter plus chemotherapy.

The trial’s primary end points were progression-free survival as evaluated by blinded independent central review based on RECIST v1.1 criteria and overall survival. ORR, DOR, adverse effects (AEs), and treatment discontinuation following AEs were secondary end points.

Patients 18 years and older with histologically or cytologically confirmed previously untreated, locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma and measurable disease according to RECIST v1.1 guidelines were able to enroll on the study. Additional eligibility criteria included adequate organ function, a life expectancy of more than 6 months, and an ECOG performance status no higher than 1.

References

  1. Agilent receives FDA approval for PD-L1 IHC 22C3 pharmDx in gastric or gastroesophageal junction (GEJ) adenocarcinoma. News release. Agilent. November 14, 2023. Accessed November 15, 2023. https://shorturl.at/ctzS2
  2. FDA approves Merck’s KEYTRUDA® (pembrolizumab) combined with trastuzumab and chemotherapy as first-line treatment in locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma. News release. Merck. May 5, 2021. Accessed November 15, 2023. https://shorturl.at/dgAFT
  3. FDA amends pembrolizumab’s gastric cancer indication. News release. FDA. November 7, 2023. Accessed November 15, 2023. https://shorturl.at/btEH7
Related Videos
Rates of obesity appear to correlate with increasing incidence of cancer in young populations, according to Monique Gary, DO, MSc, FACS.
Data from a ctDNA analysis of the phase 3 INTRIGUE study indicate that KIT mutational status may be associated with response to certain Tyrosine kinase inhibitors in GIST, according to an expert from the Yale Cancer Center in New Haven, Massachusetts.
Future research into the management of unresectable hepatocellular carcinoma may involve combining local therapies with checkpoint inhibitors like durvalumab and tremelimumab, according to Ghassan K. Abou-Alda, MD.
Patients with unresectable hepatocellular carcinoma who have recurrent disease following surgery or locally advanced diseases who will likely progress on local therapy may have an opportunity to benefit from tremelimumab and durvalumab following its FDA approval, according to Ghassan K. Abou-Alfa, MD.
Ghassan K. Abou-Alfa, MD, discusses the importance of improving access to novel therapies and combinations for patients with hepatocellular carcinoma across the world.
Ghassan K. Abou-Alfa, MD, spoke about the recent approval of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma, based on results from the phase 3 HIMALAYA trial.
Howard A. Burris, MD, highlighted previous findings of the phase 3 TOPAZ-1 trial assessing durvalumab plus gemcitabine and cisplatin vs placebo plus gemcitabine and cisplatin in advanced biliary tract cancer and patient-reported outcomes (PRO)data that were presented at 2022 ASCO.
Shubham Pant, MD discusses key findings from a basket trial examining the use of erdafitinib in patients with gastrointestinal cancers.
Related Content
FDA OKs Pembrolizumab/Chemo in HER2- Gastric/GEJ Cancer

FDA OKs Pembrolizumab/Chemo in HER2- Gastric/GEJ Cancer

November 16th 2023
Article

First-line pembrolizumab plus chemotherapy has been approved by the FDA for patients with HER2-negative gastric or gastroesophageal junction adenocarcinoma.

Experts from University of California, Los Angeles Health and Mayo Clinic discuss key data presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in the gynecologic and gastrointestinal cancer spaces and how they may impact patient care.

Oncology On-The-Go Podcast: ASCO 2023 Recap

June 19th 2023
Podcast

Experts from University of California, Los Angeles Health and Mayo Clinic discuss key data presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in the gynecologic and gastrointestinal cancer spaces and how they may impact patient care.

CHM 2101 will be assessed as part of a phase 1A/B clinical study in a population of patients diagnosed with advanced colorectal cancer, gastric cancer, and neuroendocrine cancer.

FDA Clears NDA for Novel CDH17 CAR T-Cell Therapy in Advanced GI Cancer

November 8th 2023
Article

CHM 2101 will be assessed as part of a phase 1A/B clinical study in a population of patients diagnosed with advanced colorectal cancer, gastric cancer, and neuroendocrine cancer.

Oncology Peer Review On-The-Go: Tanios Bekaii-Saab, MD, and Colleagues Discuss GOZILA Platform for CRC

Oncology Peer Review On-The-Go: Tanios Bekaii-Saab, MD, and Colleagues Discuss GOZILA Platform for CRC

May 17th 2022
Podcast

Tanios Bekaii-Saab, MD, details the GOZILA platform for colorectal cancer with experts Kristen Ciombor, MD, MSCI, and John Strickler, MD.

Results from arm A1 of the phase 2 EDGE-Gastric study indicate that patients with gastric, gastroesophageal junction, and esophageal adenocarcinoma experienced improved responses after receiving domvanalimab/zimberelimab.

Domvanalimab Plus Zimberelimab Improve Efficacy in Gastrointestinal Cancers

November 7th 2023
Article

Results from arm A1 of the phase 2 EDGE-Gastric study indicate that patients with gastric, gastroesophageal junction, and esophageal adenocarcinoma experienced improved responses after receiving domvanalimab/zimberelimab.

FDA OKs Pembrolizumab/Chemo in Advanced Biliary Tract Cancer

FDA OKs Pembrolizumab/Chemo in Advanced Biliary Tract Cancer

November 1st 2023
Article

Results from the phase 3 KEYNOTE-966 trial led to the approval of pembrolizumab plus gemcitabine and cisplatin for patients with locally advanced unresectable or metastatic biliary tract cancer.