01Jun

ASCO 2023: Head and Neck Cancer Preview

Head and Neck Cancer Preview ASCO 2023

While ASCO 2023 annual meeting is close, pharma giants, namely Merck Sharp and Dohme, Innovent Biologics, Shanghai Junshi Biosciences, and others, are looking at this opportunity to present their data readouts for different cancers, including Head and Neck Cancer. The 2023 ASCO Annual Meeting Program will offer presentations on the latest research in cancer care.

Competitive Landscape of HNC

The emerging pipeline for HNC patients consists of early-stage drugs as well as late-stage drugs in different lines of therapies  Potential therapies include xevinapant, pembrolizumab, toripalimab, and others. The emergence of several novel mechanisms of action like apoptosis proteins (IAP) antagonist, TIL cell therapy, and the mixture of naturally derived cytokines and chemokines in the HNC space has demonstrated a widespread potential as a combination or monotherapy regimen. Thus, the treatment landscape of HNC is expected to undergo a positive shift in the coming years. Let’s have a look the abstracts that we need to catchup with.

Head and Neck Cancer Highlights

 

1.     Abstract Number – LBA6002

Title: Can Sintilimab along with induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) emerge as a winner against IC-CCRT alone?

Commentary- The final abstract will be presented on the day of the presentation and would be subsequently published to the June 10, 2023 issue of Journal of Clinical Oncology.

Main Content- Patients with stage III-IVA locoregionally advanced nasopharyngeal cancer (LANPC) were included in the CONTINUUM study. Patients were randomly assigned to undergo three rounds of induction chemotherapy with gemcitabine and cisplatin, followed by cisplatin-radiation, or the same treatment with Sintilimab.

Conclusion: The effect of incorporating concurrent chemotherapy (CC) to radiotherapy (RT) following induction chemotherapy (IC) compared to IC followed by RT alone in stage II-IVB nasopharyngeal cancer (NPC) patients remains unknown in the era of intensity-modulated radiotherapy (IMRT).

 

2.     Abstract Number - 6009

Title – How would toripalimab fare against placebo in combination with gemcitabine and cisplatin?

Commentary- According to the final analysis of the Phase III JUPITER-02 trial, toripalimab plus gemcitabine and cisplatin demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to chemotherapy alone as frontline therapy in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC).

Main Content- Previously, the FDA accepted for review a biologics licence application (BLA) for toripalimab in combination with gemcitabine and cisplatin for first-line treatment of patients with recurrent or metastatic NPC, as well as as monotherapy for second-line or later treatment of patients with recurrent or metastatic NPC after platinum-based chemotherapy.

Following that, Junshi Biosciences received a comprehensive response letter to its BLA for toripalimab, demanding a modification in the quality procedure.The FDA accepted a revised BLA in July 2022 based on results from the Phase II POLARIS-02 study (NCT02915432) and the Phase III JUPITER-02 trial (NCT03581786).

Conclusion: According to the company, in comparison to chemotherapy alone, a combination comprising the immune checkpoint inhibitor toripalimab certainly has the potential to bring about extraordinary improvements in the extension of life in NPC patients.

3.     Abstract Number - 6027

Title – Does the extended treatment of  xevinapant and  radiotherapy (RT) have the ability to improvise on the efficacy?

Commentary- Xevinapant is a first-in-class, oral IAP (inhibitor of apoptosis protein) inhibitor that is intended to restore cancer cell sensitivity to apoptosis produced by radiation and chemotherapy, as well as to boost antitumor immunity. It remains to be seen if the extended treatment of xevinapant along with radiotherapy can improve the efficacy.

Main Content- When compared to a vehicle control or RT alone, Xevinapant in addition to RT (Radiotherapy) enhanced antitumor effectiveness. Furthermore, RT combined with longer xevinapant dose for 4 weeks significantly increased treatment efficacy and prolonged life when compared to RT + shorter xevinapant dosing durations. In mice treated with xevinapant + RT, FACS analysis revealed patterns of increasing numbers of CD8+ T cells, natural killer cells, and dendritic cells and decreased numbers of regulatory T cells.

Extending xevinapant dose for 4 weeks after RT increased antitumor effectiveness in preclinical mice. The findings show that the impact is controlled in part by TME responses, such as increased antitumor immunity and a decreased pro-tumorigenic phenotype of CAFs.

Conclusion: Based on these findings, more research is needed to establish the mechanisms behind the therapeutic efficacy of xevinapant prolonged dosage.

Company

Title

Trial ID

Phase

Indication

Abstract number

Innovent Biologics

PD-1 blockade with sintilimab plus induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) versus IC-CCRT in locoregionally-advanced nasopharyngeal carcinoma (LANPC): A multicenter, Phase III, randomized controlled trial (CONTINUUM)

NCT03700476

III

HNC

#LBA6002

Merck

Effect of extended treatment with IAP inhibitor xevinapant post radiotherapy (RT) on efficacy and the tumor microenvironment (TME) in preclinical models

NCT05386550

III

HNC

#6027

Shanghai Junshi Bioscience

Final overall survival analysis of JUPITER-02: A phase 3 study of toripalimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC)

NCT03581786

III

HNC

#6009

Merck Sharp & Dohme

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with pembrolizumab and carboplatin as first-line treatment of recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC): A singlearm, phase 2 trial

NCT04643379

II

HNC

#6016

Astellas Pharma

Enfortumab vedotin in the previously treated advanced head and neck cancer (HNC) cohort of EV-202

NCT04225117

II

HNC

#6017

Elevar Therapeutics

Updated results from a phase 2 study of the oral vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor rivoceranib for recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC)

NCT04119453

II

HNC

#6040

Immutep

Final results from TACTI-002 Part C: A Phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with metastatic 2nd line head and neck squamous cell carcinoma unselected for PD-L1

NCT03625323

II

HNC

#6029

PDS Biotechnology Corp

Safety and efficacy of immune checkpoint inhibitor (ICI) na¨ıve cohort from study of PDS0101 and pembrolizumab in HPV16-positive head and neck squamous cell carcinoma (HNSCC)

NCT04260126

II

HNC

#6012

Sichuan Baili Pharmaceutical

Results from two phase II studies of SI-B001, an EGFR3HER3 bispecific antibody, with/without chemotherapy in patients (pts) with recurrent and metastatic head and neck squamous cell carcinoma (HNSCC)

NCT05044897/NCT05054439

II

HNC

#6037

Zhejiang Genfleet Therapeutics

A phase Ib/II study of GFH018 in combination with toripalimab in recurrent/ metastatic nasopharyngeal carcinoma (R/M NPC)

NCT04914286

I/II

HNC

#6026

Jiangsu HengRui Medicine

A pilot phase II trial of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin (NeoCPC) for locoregionally advanced, resectable squamous cell carcinoma of the head and neck

NCT04826679

II

HNC

#6069