The potential of PD-1/PD-L1 neoadjuvant therapy is gradually showing. Who will become the first "dark horse" in China?

Today, the emergence of PD-1/PD-L1 inhibitors has brought tremendous progress in the treatment of tumors.

With the deepening of clinical applications, PD-1/PD-L1 inhibitors have begun to be used in early-stage tumor patients, and they have once again shined in the neoadjuvant treatment of cancer patients.

Tumor patients are generally in a state of immunosuppression.

For multiple tumor types,

PD-1 new assistant shows positive results

In 2018, Forde and others took the lead in reporting the first clinical study of neoadjuvant immunotherapy in the New England Journal.

The results showed that at 18 months, the recurrence-free survival rate was 73%.

The positive data of this research has set off a global upsurge of neoadjuvant immunotherapy.

At present, the neoadjuvant immunotherapy of PD-1/PD-L1 inhibitors has been applied to non-small cell lung cancer, and has also entered clinical research on many cancers such as glioma, bladder cancer, head and neck cancer, melanoma, etc.

For glioma, a multicenter, randomized, open-label clinical study showed that patients who received neoadjuvant therapy (Pembrolizumab, Pembrolizumab) had progression-free survival compared with patients without neoadjuvant therapy (PFS) and overall survival (OS) were significantly improved.

For bladder cancer, a single-arm, phase II, open study (PURE-01 trial) of pembrolizumab showed that pembrolizumab may be a PD-L1 positive or high TMB muscular infiltrating bladder An effective program for neoadjuvant therapy before surgery for cancer patients.

For head and neck cancer, an open, multi-center, phase I/II clinical trial (CheckMate 358) for nivolumab enrolled 29 patients.

In addition, a phase II clinical trial for pembrolizumab (NCT02296684) showed that for HPV-negative, stage III/IV head and neck squamous cell carcinoma patients using pembrolizumab neoadjuvant therapy, 43% Of patients achieved pathological remission >10%, and 48% of patients had a decline in clinical and pathological stages.

Immune combination therapy has also achieved positive clinical results in neoadjuvant therapy, especially immune combination chemotherapy.

The NADIM clinical study for lung cancer showed that after 3 courses of nivolumab combined with chemotherapy (carboplatin + paclitaxel), 65% of patients could not find cancer cells at all, and 15% of patients had cancer cells in 10%.

Domestic companies have begun to deploy,

Who will become the first "dark horse"?

In recent years, my country's PD-1/PD-L1 inhibitor neoadjuvant therapy clinical research is also in full swing.

The Insight database shows that a number of neoadjuvant treatments for PD-1/PD-L1 inhibitors in China have entered the late clinical stage, involving 5 PD-1 and 3 PD-L1.

Among the domestic varieties, Hengrui’s Karelizumab, Junshi’s Tereprizumab and Fuhong Henlius’s Slulizumab have all carried out adjuvant/neoadjuvant treatment clinical trials for triple-negative breast cancer.

As of April 25, Insight database mapping

For PD-L1, Roche’s atezizumab (T drug) and AstraZeneca’s duvalizumab (I drug) have carried out more adjuvant/neo-adjuvant clinical trials, but the current domestic Oncology's ZKAB001 initiated a phase I/II clinical trial for esophageal squamous cell carcinoma.

As of April 25, Insight database mapping

With the deepening of research on neoadjuvant immunotherapy, there will surely be more clinical programs at home and abroad in the future.
From the current clinical research data, neoadjuvant immunotherapy can bring greater therapeutic benefits to patients, and has comparative advantages compared to chemotherapy, showing its huge development prospects.

my country has not yet launched a neoadjuvant immunotherapy program, but a number of neoadjuvant immunotherapy clinical studies have entered the late clinical stage.
Who will be the first to obtain positive data and become the first dark horse to be marketed? let us wait and see.