ASCO 2021 preview: News drugs from Yuhan, Genexin, and Hanmi

ASCO 2021 virtual annual meeting to be held from June 4th to 6th… abstracts pre-released

ASCO 2019 학회 전경(자료: ASCO)

The organizers of the 2021 ASCO Annual Meeting (ASCO 2021) released the accepted abstracts on the 19th (local time), two weeks ahead of the virtual event that will be held next month, from June 4-8.

 

The ASCO meeting is considered one of the most important events for biopharmaceutical companies around the world in introducing the latest clinical data on anticancer drugs.

 

Due to the COVID-19 pandemic, all schedules in the 5-day event, including its keynote lectures, poster sessions, and exhibitions will be held virtually, non-face-to-face, for the second consecutive year.

 

The abstracts of Korean biopharmaceutical companies including Yuhan Corporation, Hanmi Pharmaceutical, MedPacto, and Genexin that have been developing new anticancer drugs have also been unveiled with the pre-release.

 

Whether the long-awaited international event will be able to rekindle investors’ interest in the biopharmaceutical industry is drawing attention.

 

At the event, the multinational pharmaceutical company Janssen will be presenting 2 studies on the combination of its EGFR/cMET dual antibody ‘amivantamab’ and Yuhan Corporation’s new drug ‘Leclaza (lasertinib).’ The abstracts are an update from the Phase 1b CHRYSALIS study that received much attention at the ESMO 2020 Meeting last year.

 

The abstract focuses on the potential of the combination in overcoming the resistance issue of its competitor ‘Tagrisso (osimertinib).’ The study focused on delaying cancer progression through treatment with amivantamab in combination with Leclaza in patients with non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) exon 19 deletion or L858R mutations who have acquired resistance to Tagrisso.

 

The study focused on analyzing the biomarkers while conducting genetic testing through next-generation sequencing (NGS) in circulating tumor DNA (ctDNA) to profile each patient’s tumor.

 

If each patient’s response rate could be predicted in advance, this could maximize the response rate of the amivantamab and Leclaza combination therapy.

 

Results showed that among the 45 patients whose disease had progressed on osimertinib that were administered 240mg of Leclaza and 1050mg or 1400mg of the amivantamab and Leclaza combination, the ORR(objective response rate) was 36% (95% CI, 22–51), with 1 patient showing complete response and 15 showing partial responses.

 

Up to this, the data presented were similar to those presented at the ESMO 2020 last year.

 

However, the investigators additionally presented an analysis of potential biomarkers of response.

 

According to the analysis, 8 out of the 17 patients with EGFR and/or MET-based mutations – which is known to be the cause of resistance to Tagrisso – showed a confirmed tumor response.

 

The median progression-free survival (PFS) of these patients was 6.7 months (3.4months- not reached).

 

However, as some (8 patients) of the 18 patients who had unknown mechanisms of Tagrisso-resistance also showed a partial response to the regimen, grounds for its use as a biomarker was seen to be insufficient.

 

9 out of 10 Immunohistochemistry (IHC) high patients (90%) showed a high response rate to treatment, but the abstract determined that further investigation is warranted.

 

More progressed data on the study will be shared at the oral abstract session for metastatic non-small cell lung cancer on the 5th, the second day of the meeting.

 

The principal investigator of the Phase III LASER301 trial, Professor Byoung Chul Cho (Director of the Lung cancer center, Yonsei Cancer Center), will be presenting the session.

 

Genexin released an abstract on the interim results of its Phase 2 clinical trial that evaluated the combination of its cervical cancer DNA vaccine 'GX-188E' with Merck(MSD)’s immunotherapy ‘Keytruda(pembrolizumab).’ The abstract contained results of the efficacy group of patients with late-stage recurrent or advanced HPV-positive (HPV-16 or HPV-18) cervical cancer.

 

5 of the 48 patients had a complete response (CR) where the target lesion completely disappeared, and 10 had a partial response (PR) where the target lesion was reduced by 30% or more.

 

The objective response rate (ORR) was 31.3%.

 

Subanalysis results showed that the ORR of patients with PD-L1 positive, HPV-16, and squamous cell carcinoma was highest, being 48%.

 

The combination therapy showed an improved median PFS of 4.1 months, and OS of 16.7 months compared to Keytruda monotherapy.

 

Most of the patients who experienced adverse events showed grade 1 or 2 adverse events, demonstrating that there were no safety issues concerning to the combination therapy.

 

The details of the GX-188E and Keytruda combination will be introduced at the oral abstract session on the first day of the ASCO meeting, on the 4th (local time).

 

MedPacto released the Phase 1b/2a trial results of ‘vactosertib’ (capecitabine)’ combined with ‘Keytruda’ in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients.

 

According to the abstract, 5 of the 33 patients enrolled in the trial reached PR, and the ORR was 15.2%.

 

7 patients had stable disease where the tumor did not grow further.

 

Industry has seen that the study fully demonstrated the potential of vactosertib as a combination option in MSS mCRC as the response rate of Keytruda monotherapy is near 0% for the disease.

 

Further clinical data on more patients and the OS data and doses will also be released in the final poster that will be released on the 4th (local time).

 

Hanmi Pharmaceutical has released the latest update on ‘belvarafenib,’ which was licensed to Genentech.

 

The results are from a Phase I trial of belvarafenib in combination with cobimetinib in patients with BRAF- and NRAS-mutant melanoma.

 

The abstract shows further progress that had been made since the last presentation at the 2019 ASCO meeting.

 

According to the abstract, 5 of the 13 NRAS-mutant melanoma patients reached PR, giving an ORR of 38.5%.

 

Currently, no approved standard of care exists for NRAS-mutant melanoma.

 

According to clinicaltrials.gov, a clinical trial registration website operated by the U.S.

 

National Institute of Health (NIH), Genentech had recently registered a new global Phase I clinical trial on belvarafenib.

 

The Phase 1b study will evaluate the safety, pharmacokinetics, and activity of belvarafenib as a single agent and in combination with either ‘Cotelic (cobimetinib) or Cotelic plus ‘Tecentriq (atezolizumab)’ in patients with NRAS-mutant advanced melanoma who have previously received anti-PD-1/PD-L1 therapy.

 

As this is the first clinical trial initiated for a belvarfenib combination therapy by Genetech in 5 years since singing the technology transfer deal with Hanmi Pharmaceutical, concerns over the deal cancellation have been said to be resolved.

 

Analysts predict that if the three-dug combo including belvarafenib shows a superior response rate over ‘Zelboraf,’ the new drug’s value may increase additionally.