As the 2024 American Society of Clinical Oncology (ASCO) annual meeting approaches, excitement builds over the latest in cancer treatment advancements. From May 31 to June 4, industry leaders will unveil new data on different therapies. Leading pharmaceutical companies, including AstraZeneca, Daiichi Sankyo, Merck, Cue Biopharma, Hookipa Biotech, AffyImmune Therapeutics, Nanjing Leads Biolabs, Seagen, Genmab, and others are prepared to unveil the eagerly anticipated results as ASCO 2024 draws to a close, and are looking at this opportunity to present their innovations in Head and Neck Cancer. 

In the upcoming presentations on Head and Neck Cancer (HNSCC), Merus will shed light on petosemtamab + pembrolizumab in first-line treatment, along with insights on MCLA-145 +/- pembrolizumab in solid tumors. In Addition, AstraZeneca will share findings on Trastuzumab deruxtecan (T-DXd) from DESTINY-PanTumor02's head and neck cohorts (#6037). Hookipa Biotech's focus will be on HB-200 combined with pembrolizumab as a first-line therapy for HPV16+ HNSCC. These presentations hold significant promise, especially when considering the outcomes from DESTINY-PanTumor02 (DP-02) and the updated results of HB-200 combined with pembrolizumab alongside the Phase Ib/II dose escalation/expansion study of LBL-007.

Abstract Summary

1. Abstract Number – 6037

Title: AstraZeneca and Daiichi Sankyo to Unveil DESTINY-PanTumor02 study results on trastuzumab deruxtecan in treating HER2-expressing head and neck cancer

Commentary - ENHERTU’s clinical success and regulatory progress establish it as a pioneering treatment for HER2-expressing head and neck cancer.

Executive Summary – ENHERTU (fam-trastuzumab deruxtecan-nxki), formerly known as DS-8201, is the lead product in the antibody–drug conjugate (ADC) franchise of the Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC Scientific platform. ASCO conference will feature pivotal findings from the DESTINY-PanTumor02 study.

Main Content –  

ENHERTU (trastuzumab deruxtecan), developed with Daiichi Sankyo’s DXd ADC technology, has shown promising results in an interim analysis of the ongoing DESTINY-PanTumor02 Phase II trial. It exhibited meaningful and lasting responses across various HER2-expressing advanced solid tumors in previously treated patients. DESTINY-PanTumor02, a global Phase II trial, is assessing ENHERTU's efficacy and safety in previously treated HER2-expressing tumors, including head and neck cancer. Primary endpoints include confirmed objective response rate, with secondary endpoints covering the duration of response, disease control rate, progression-free survival, overall survival, safety, tolerability, and pharmacokinetics.

Trastuzumab deruxtecan has already received accelerated approval for tumor-agnostic use, partially based on the results of the PanTumor02 trial in HER2-positive solid tumors. While these presentations at ASCO may not be the primary focus for investors, they offer valuable commercial insights. Of particular interest to investors will be updated survival data, pivotal in securing confirmatory approval.

Conclusion: ENHERTU shows promise in HER2-expressing advanced solid tumors in the ongoing DESTINY-PanTumor02 Phase II trial. This global study assesses ENHERTU's effectiveness and safety in previously treated HER2-expressing tumors, including head and neck cancer, with a primary focus on objective response rate. The interim analysis suggests potential for tumor-agnostic application, and ASCO presentations offer vital commercial insights, particularly on updated survival data.

2. Abstract Number – 6005

Title:  Hookipa Biotech is set to present an oral session on HB-200 combined with pembrolizumab as the first-line treatment for HPV16+ head and neck squamous cell carcinoma (HNSCC) at ASCO.

Commentary – HB-200 combined with pembrolizumab, shows promising results for first-line treatment of recurrent/metastatic HPV16+ head and neck cancer, doubling response rates compared to pembrolizumab alone. Based on these encouraging results, HOOKIPA is gearing up to initiate a pivotal trial of HB-200 in 2024.

Executive Summary – Additional data on HB-200 combined with pembrolizumab will be presented at the ASCO 2024 Annual Meeting's Head and Neck Oral Abstract Session. This presentation will reveal preliminary progression-free survival and overall survival data for the first time, reinforcing the company's confidence in achieving its goals and offering a new targeted therapy for patients with HPV16+ head and neck cancer. Aligning the trial with primary regulators can expedite potential registration.

Main Content – Hookipa Biotech’s lead oncology candidate, HB-200, engineered with their proprietary replicating arenaviral vector platform, has shown promising preliminary results. Comprising two single-vector compounds based on lymphocytic choriomeningitis virus (LCMV) and pichinde virus (PICV), HB-200 expresses an E7E6 fusion protein derived from HPV16. In combination with pembrolizumab, HB-200 has received Fast Track Designation from the US FDA and PRIME designation from the European Medicines Agency for first-line treatment of HPV16+ recurrent/metastatic oropharyngeal squamous cell carcinoma.

Hookipa Biotech will present Phase I/II trial (NCT04180215) results at ASCO 2024, focusing on HB-200 combined with pembrolizumab as a first-line treatment for HPV16+ HNSCC. This follows data from ESMO 2023 showing a 42% ORR in CPS ≥ 1 HPV+ HNSCC, doubling the ORR seen with pembrolizumab monotherapy. The updated dataset will include more patients, potentially 35-40, to provide greater confidence. Investors will be keenly focused on durability data to validate the T-cell activating mechanism and demonstrate HB-200's potential to outperform pembrolizumab monotherapy in Phase III trials and commercial use.

Additionally, Hookipa will present data on HB-200 combined with chemotherapy as a neoadjuvant therapy for HPV16+ oropharyngeal cancer. These updates are crucial for Hookipa to gain investor momentum and avoid delisting after receiving a NASDAQ Deficiency Notice. Positive results will help the company return to compliance and bolster investor confidence.

Conclusion:  Hookipa Biotech will present promising Phase I/II (NCT04180215) results for HB-200 combined with pembrolizumab as a first-line treatment for HPV16+ HNSCC. This presentation will showcase data from around 40 patients, highlighting the combination's safety and early efficacy, suggesting the need for further study. Additionally, early signals show that neoadjuvant HB-200 plus chemotherapy is safe and feasible for HNSCC patients.

3. Abstract Number –  6014

Title: Merus secures rapid oral presentation slot to reveal interim results of petosemtamab + pembrolizumab in first-line HNSCC at ASCO Annual Meeting

Commentary – Merus’ petosemtamab + pembrolizumab interim analysis sparks hope for first-line HNSCC patients, showing promising activity across tumor PD-L1 expression levels and HPV Status, alongside encouraging safety profile.

Executive Summary – In a groundbreaking development, the combination of Petosemtamab, a pioneering EGFR x LGR5 bispecific antibody, with pembrolizumab showcases a well-tolerated safety profile and offers promising initial clinical efficacy. This exciting advancement heralds a potential first-line treatment option for patients battling recurrent/metastatic head and neck squamous cell carcinoma.

Main Content – 

With the incidence of HNSCC projected to surge significantly by 2030, the need for effective treatments is urgent. Petosemtamab, an innovative bispecific antibody targeting EGFR and LGR5, holds promise in this regard. Combined with pembrolizumab, it demonstrates potential as a first-line therapy for HNSCC.

The recent breakthrough therapy designation granted by the US FDA underscores the significance of petosemtamab in addressing recurrent or metastatic HNSCC. Supported by encouraging data from ongoing trials, including Phase II investigations, this designation marks a significant step forward.

At the upcoming ASCO conference, a rapid oral session will spotlight the Phase I/II data unveiling the efficacy and safety of petosemtamab. 

Looking ahead, Merus is poised to advance into Phase III trials, aiming to assess petosemtamab's efficacy in previously treated HNSCC cases and explore its potential in combination with pembrolizumab for previously untreated patients. These developments signal a promising trajectory in the quest for improved outcomes in HNSCC treatment.

Conclusion: Despite recent advancements, head and neck squamous cell carcinoma remains a deadly disease with limited treatment options. However, the combination of petosemtamab and pembrolizumab holds promise as a potential breakthrough, poised to establish a new treatment standard for previously untreated head and neck cancer patients.

4. Abstract Number –  6033

Title: The anti-LAG-3 antibody LBL-007, when combined with an anti-PD-1 antibody, offers enhanced benefits for patients battling advanced nasopharyngeal cancer and other malignancies.

Commentary - Nanjing Leads Biolabs is set to unveil groundbreaking clinical research data at a poster session. They will showcase the safety and effectiveness of their monoclonal antibody LBL-007, which targets lymphocyte activation gene-3 (LAG-3), in combination with toripalimab for treating patients with advanced malignant tumors

Executive Summary – LBL-007, in combination with toripalimab, is well-tolerated in patients with advanced malignant tumors and has demonstrated encouraging preliminary efficacy, both in patients with advanced NPC with or without prior anti-PD-(L)1 therapy.

Main Content –  

LBL-007, a fully human monoclonal antibody targeting LAG-3, has demonstrated encouraging outcomes in preclinical trials. It exhibits specific binding to human LAG-3, triggers IL-2 release, and curbs tumor growth in animal models by impeding LAG-3 binding to MHC II and other ligands.

In December 2021, Nanjing Leads Biolabs and BeiGene established a collaboration, granting BeiGene global rights for research, development, manufacturing, and an exclusive commercialization outside of China for LBL-007.

During ASCO, the Phase Ib/II clinical study will present compelling data on the efficacy and safety of LBL-007 in tandem with anti-PD-(L)1 monoclonal antibody, with a particular focus on treating NPC. This multicenter study in China enrolled patients with various advanced malignant tumors, including nasopharyngeal carcinoma. By December 2023, the study showed an objective response rate of 33.3% and a disease control rate of 75.0% in NPC patients without prior immunotherapy. These findings underscore the well-tolerated nature of LBL-007 combined with toripalimab, highlighting promising preliminary efficacy in patients with advanced malignant tumors, irrespective of prior anti-PD-(L)1 therapy. This Phase Ib/II dose escalation/expansion study represents a significant leap forward in cancer therapy.

Conclusion: 

LBL-007, a promising monoclonal antibody targeting LAG-3, has shown encouraging preclinical results. Collaborative efforts between the upcoming ASCO presentations of Phase Ib/II data underscores its potential as a groundbreaking therapy, particularly in NPC treatment, marking a significant advancement in cancer care.