Korean bio-pharma companies attract attention at AACR 2021

Domestic biopharma companies present potential of combination therapies and preclinical studies

AARC holds Annual Meeting on Novel Approaches to Enhance Immunotherapy … combination therapies receive attention

The AACR 2021 Annual Meeting, the largest meeting on cancer research in the world, took place from April 10th to April 15th.

 

At the meeting, new combination therapies were introduced, raising expectations for the use of new mechanisms of action in the field of cancer treatment.

 

Through a presentation of data on the use of nivolumab (Opdivo) in early-stage non-small cell lung cancer (NSCLC), Bristol Myers Squibb (BMS) presented its next target area for its PD-1/L1 inhibitor.

 

Bayer appealed the efficacy of its PI3K inhibitor copanlisib (Aliqopa) in combination with rituximab.

 

Results of Combination therapy studies show potential to expand treatment scope The presentation that first drew attention was the latest clinical data on Opdivo, which was one of the first PD-1 inhibitors approved in the field of immuno-oncology.

 

Patients with early-stage NSCLC who received the Opdivo-chemotherapy combination before surgery were nearly 14 times more likely to show no signs of cancer cells in their resected tissue than those who received only chemotherapy.

 

The findings came from the Phase III CheckMate-816 trial, which enrolled patients with stage IB to IIIA NSCLC.

 

BMS explained that this was the first time for a presurgery use of the Opdivo-chemotherapy combination to show a significant improvement in the complete pathological response in patients with earlier stage NSCLC More specifically, 24% of patients receiving the Opdivo-chemotherapy combination had a pathological complete response (pCR) which was defined as no residual viable tumors in their resected tissues and lymph nodes, compared with 2.2% in the chemotherapy alone arm, Also, pathological response in patients in the Opdivo combination group was 36.9%, significantly higher than the 8.9% in the chemotherapy alone group.

 

Patrick Forde, professor at Johns Hopkins University said, “For the first time in a phase III trial, we see the potential for an anti-PD-1 immunotherapy to improve outcomes in earlier-stage NSCLC.

 

We are highly encouraged by the marked improvement in pCR, the overall good tolerability, and the absence of impact on surgery feasibility when nivolumab is added to neoadjuvant chemotherapy,”

Bayer had presented the role of PI3K inhibitors in treating patients with indolent non-Hodgkin’s lymphoma (iNHL) who relapsed after at least one prior therapy with the combination of its copanlisib (Aliqopa) and rituximab (Rituxan).

 

The data was from the Phase III Chronos-3 trial, in which patients were randomly assigned to copanlisib-rituximab combination (307 patients) or placebo-rituximab combination (151 patients) After a median follow-up of 19.2 months, the study met its primary endpoint of progression-free survival (PFS), showing a 48% reduction in the risk of lymphoma progression or death in the copanlisib-rituximab arm.

 

The overall response rate (ORR) was 80% in the copanlisib-rituximab arm and 47.7% in the placebo-rituximab arm.

 

The complete response rate (CRR) was 33.9% in the copanlisib-rituximab arm, compared to the 14.6% in the placebo-rituximab arm.

 

Regarding the results, Bayer stated that Aliqopa was the first PI3K inhibitor to demonstrate superior efficacy in combination with Rituxan with a manageable safety profile in patients with relapsed iNHL.

 

Also, Lilly presented the potential of its Retevmo to be approved for indications other than those reived for lung cancer and thyroid cancer with RET abnormalities.

 

At the annual meeting, Lilly announced that Retevmo shrunk tumors in 47% of patients with RET fusion-positive cancers originating from different sites in the body other than the lung and the thyroid in a Phase 1/2 study.

 

In particular, Lilly emphasized that more than half of the patients still showed benefits after a median follow-up of 13 months.

 

The 47% tumor response rate presented at the 2021 AACR was generated from 32 patients that had 12 unique cancer types with RET fusion.

 

Over 60% of patients had treatment-resistant gastrointestinal cancers that typically do not respond well to targeted therapy.

 

Based on such data, the company said it plans to take the ‘tumor agnostic' approach with Retevmo.

 

 

Increasing the response rate with combination therapies…compatibility between candidate substances?

 

Clinical research by domestic biopharmaceutical companies presented at AACR mostly ended at preclinical trial outcomes or examining the potential of combination therapies.

 

However, some showed promise by drawing a response rate from patients that did not respond to existing drugs.

 

At the poster session held on the 12th, PharmAbcine presented the nonclinical data of its immune-oncology drug candidate PMC-309.

 

PMC-309 is showing promise as an immunotherapeutic strategy to be used alone or in combination for patients who showed no response to existing immune-oncology drugs by inhibiting a new immune checkpoint.

 

PMC-309 is a monoclonal IgG (Immunoglobulin G) that targets human VISTA (V-domain Ig Suppressor of T cell Activation), an immune checkpoint regulator.

 

The nonclinical study results show that PMC-309 increased T cell activities in in-vitro settings with its anti-VISTA effect.

 

In in vivo studies using a human VISTA Knock-In mouse model, the tumor growth inhibition was significantly higher for the PMC-309 group compared to the control group.

 

The tumor growth inhibition rate was comparable to the PD-1 administered group and showed a possible synergistic effect when used in combination with existing immunotherapy.

 

The company plans to evaluate the potential toxicity risk of PMC-309 this year to submit for the IND (Investigational New Drug)-enabling studies, and expects to enter the clinical stage next year.

 

ABL Bio presented the preclinical trial results of its bispecific antibody dual immune checkpoint blockade that includes the target LAG-3, an emerging next-generation immuno-oncology drug.

 

ABL501 is a bispecific antibody that simultaneously targets both PD-L1 and LAG-3.

 

Recently, BMS announced successful results of a Phase II/III trial using its anti-LAG-3 antibody(elatlimab) in combination with its PD-1 inhibitor (nivolumab) in patients with melanoma, bringing the candidate substance one step closer to commercialization.

 

In-vitro and in-vivo assessments of the drug demonstrated that ABL501 showed better anti-tumor effect than the PD-L1and LAG-3 combination therapy.

 

With such positive results, the drug was evaluated to have potential as a new alternative to patients who did not see an effect with existing PD-1 or PD-L1-based therapies.

 

ABL Bio plans to submit a Phase 1 Investigational New Drug Application (IND) based on the data.

 

MedPacto presented the potential to use its immune-oncology drug Vactosertib as a combination therapy.

 

The combination of Vactosertib and Onivyde was found to significantly reduce metastasis of cancer cells and greatly improved survival rates compared to Onivyde alone.

 

In the 50-day study of the combination using animal models, the survival rate of the group that was not administered Vactosertib and the group that used the current established treatment was 23% and 53% respectively.

 

However, the Vactosertib combination group’s survival rate improved to reach 84%.

 

This suggests the potential of the combination as a new treatment option.

 

Also, Qurient announced the results for its CDK-7 inhibitor ‘Q901’ and received attention for its potential as an alternative for patients developing resistance.

 

Although the study is yet in its in-vivo stages, Q901 showed tumor growth inhibition effect in mice that developed resistance to the CDK4·6 inhibitor (Ibrance), suggesting its potential in patients who developed resistance to existing breast cancer treatments that may found in clinical studies in the future.