First-in-human study of BG-C9074, a B7-H4-targeting ADC in patients with advanced solid tumors:Preliminary results of the dose-escalation phase

Videos

Presented by Dr. Cesar Perez, this first-in-human phase 1 study of BG-C9074—a B7-H4–targeting antibody-drug conjugate—demonstrated early antitumor activity and a manageable safety profile in heavily pretreated patients with advanced solid tumors.

First-in-human study of BG-C9074, a B7-H4-targeting ADC in patients with advanced solid tumors: Preliminary results of the dose-escalation phase

Cesar A. Perez, MD, discusses the ongoing investigation of frontline petosemtamab plus pembrolizumab in head and neck squamous cell carcinoma.

Dr Perez on the Efficacy and Safety of Frontline Petosemtamab Plus Pembrolizumab in HNSCC

Cesar A. Perez, MD, director, drug development, Sarah Cannon Research Institute, Florida Cancer Specialists & Research Institute; associate professor, medicine, University of Miami; discusses the ongoing investigation of frontline petosemtamab (MCLA-158) plus pembrolizumab (Keytruda) in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Data from a phase 2 trial (NCT03526835) evaluating the combination in 24 efficacy-evaluable patients with previously untreated, recurrent or metastatic PD-L1–positive HNSCC were presented at the 

. The combination demonstrated an overall response rate (ORR) of 67% (95% CI, 45%-84%), comprising 1 complete response (CR), 12 partial responses (PRs), and 3 unconfirmed PRs, which is substantially higher than the expected response rate with pembrolizumab alone.

Responses occurred in different patient subgroups, including those who were HPV-positive and HPV-negative, as well as across PD-L1–high and PD-L1–low populations. Specifically, 42% of patients had a PD-L1 combined positive score (CPS) of 1 to 19, and 56% had a PD-L1 CPS of 20 or higher. Among patients with a low PD-L1 CPS, the ORR was 60%. Best response to treatment included 2 cases of progressive disease (PD), 2 cases of stable disease (SD), 1 unconfirmed PR, 4 PRs, and 1 CR. For patients with a high PD-L1 CPS, the ORR was 71%, with 1 case of PD, 3 instances of SD, 2 unconfirmed PRs, and 8 PRs as the best responses. Additionally, among patients with HPV type 16 (57%) and those without (36%), the ORRs were 75% and 65%, respectively.

Regarding safety, no new safety signals were observed with the combination of petosemtamab and pembrolizumab, Perez details. Adverse effects (AEs) were as expected, with infusion reactions occurring in 38% of participants. Notably, 7% of these reactions were grade 3, and there were no grade 4 or 5 infusion reactions. Other AEs included known effects of EGFR targeting, such as cutaneous reactions, low magnesium levels, and fatigue. These AEs were manageable, and the absence of new safety signals was encouraging.

Despite the relatively short follow-up and small cohort size, these findings are promising, Perez states. Responses were observed early, often at the first response assessment, and clinical improvement was typically seen after the first infusion, he details. This rapid onset of response is particularly significant for a chemotherapy-free regimen, Perez emphasizes.

Overall, the combination of petosemtamab and pembrolizumab holds potential for changing the treatment paradigm for PD-L1–positive HNSCC since more patients may be potential candidates for a chemotherapy-free regimen, Perez says. High response rates and a longer duration of response could lead to significant improvements in overall survival. Future studies and longer follow-up will be essential to confirm these findings and to further evaluate the efficacy and safety of this combination therapy, he concludes.

Cesar A. Perez, MD, discusses the ongoing investigation of frontline petosemtamab plus pembrolizumab in head and neck squamous cell carcinoma.

Cesar Augusto Perez, MD, medical oncologist, director, Drug Development, Florida Cancer Specialists & Research Institute, Sarah Cannon Research Institute, discusses the potential utility of KIN-2787 in 

KIN-2787 is an investigational, next-generation, pan-RAF inhibitor being evaluated for patients with solid tumors harboring class I, II, and III 

 mutations, Perez explains. The agent was specifically developed to target class II and III mutations, which is an area of significant unmet need in patients with 

KIN-2787 is being evaluated in an ongoing phase 1 trial (NCT04913285) for adult patients with 

-mutated solid tumors, including non–small cell lung cancer and melanoma, Perez says. This drug is unique because most available agents for patients with 

-mutated diseases were designed to target class I mutations. As such, the results of this study will be intriguing as KIN-2787 could have clinical utility across 

 mutation–positive subgroups, Perez concludes. 

Cesar Augusto Perez, MD, discusses the potential utility of KIN-2787 in BRAF-mutated solid tumors. 

Cesar Augusto Perez, MD

Articles

First-in-human study of BG-C9074, a B7-H4-targeting ADC in patients with advanced solid tumors: Preliminary results of the dose-escalation phase

Dr Perez on the Efficacy and Safety of Frontline Petosemtamab Plus Pembrolizumab in HNSCC

Dr. Perez on the Potential Utility of KIN-2787 in BRAF-Mutated Solid Tumors