'Keytruda' and 'Tecentriq' Maximize Immuno-Oncology Efficacy... Developers Embrace Combination Therapy

Fighting Cancer with Combination Therapy
Domestic Companies Join Forces with Merck and Roche
to Accelerate Development

[Asia Economy, Lee Chunhee] Eleven years have passed since Bristol-Myers Squibb's 'Yervoy' (ingredient: ipilimumab), the first immuno-oncology drug, received approval from the U.S. Food and Drug Administration (FDA). Although these drugs have shown remarkable results, such as significantly improving survival rates, a major drawback remains: their effectiveness is limited to only a subset of patients. This is why various combination therapies are being explored both domestically and internationally to overcome these limitations.

Fighting Cancer with Combination Therapy

According to industry sources on July 8, the global immuno-oncology drug market is expected to grow explosively from $74.7 billion (about 97 trillion won) in 2020 to $159.5 billion (about 207 trillion won) by 2027.

The mainstream of immuno-oncology drugs is immune checkpoint inhibitors. These drugs overcome the shortcomings of traditional anticancer agents, which attack normal cells as well. Cancer cells send signals to immune checkpoints to indicate they are not intruders, thereby preventing immune cells from attacking them. Immune checkpoint inhibitors block this disguise strategy, enabling immune cells to destroy cancer cells and thus demonstrating strong efficacy.

However, a persistent drawback of immuno-oncology drugs is their low 'objective response rate (ORR),' which is the proportion of patients whose tumors shrink or disappear after treatment. In fact, there are more patients who do not respond to the drugs at all than those who do, and for certain types of cancer, the drugs may not be effective for anyone.

MSD (Merck & Co., USA)'s immuno-oncology drug Keytruda and Roche's immuno-oncology drug Tecentriq

Nevertheless, cases have been observed where the ORR increases dramatically when immuno-oncology drugs are administered in combination with other medications. As a result, combination therapy is emerging as a promising strategy to maximize the effectiveness of immuno-oncology drugs. An industry insider who attended the American Society of Clinical Oncology (ASCO) meeting last month stated, "When I was there, it was clear that combination therapy had already become the dominant trend. Of course, studies on monotherapy are still ongoing, but there was a general consensus that combination therapy is more effective."

This is why, despite the lack of successful development of immuno-oncology drugs themselves in Korea, many companies are actively pursuing combination therapy development. Global big pharma companies that have already launched immuno-oncology drugs are also actively supporting research on combination therapies.

Domestic Companies Collaborate Actively with MSD and Roche

The majority of combination therapy research is being conducted with MSD (Merck & Co., USA)'s 'Keytruda.' In Korea alone, various companies such as NeoImmuneTech, MedPacto, and NKMax are working on developing combination therapies.

NeoImmuneTech recently presented interim results from a Phase 2a clinical trial of its T-cell amplifier 'NT-I7' in combination with Keytruda for microsatellite stable (MSS) colorectal cancer and pancreatic cancer at the ESMO Gastrointestinal Cancers Congress, organized by the European Society for Medical Oncology. MSS colorectal cancer has previously shown a 0% objective response rate (iORR) with Keytruda monotherapy, and pancreatic cancer has also shown no effect. NeoImmuneTech reported that, with combination therapy, the iORR reached 11.1% for MSS colorectal cancer and 7.7% for pancreatic cancer.

MedPacto is also conducting combination studies of 'Vactosertib' and Keytruda targeting MSS colorectal cancer and pancreatic cancer. The company plans to begin global Phase 3 clinical trials for colorectal cancer in the United States and elsewhere soon. For pancreatic cancer, it intends to submit a clinical trial application for accelerated approval within the third quarter.

NKMax is targeting non-small cell lung cancer. In a long-term follow-up comparing its immuno-oncology drug 'SuperNK (SNK01)' in combination therapy to Keytruda monotherapy, the overall survival (OS) rate at two years was 41.6% higher in the combination group. Seven out of twelve patients in the combination group survived, whereas all six patients in the monotherapy group died. In addition, Genome & Company (cholangiocarcinoma), PharmAbcine (triple-negative breast cancer), and Genexine (cervical cancer) are also preparing for combination therapy with Keytruda.

In addition to Keytruda, Roche's 'Tecentriq' (ingredient: atezolizumab) is also one of the main targets for combination therapy research. NeoImmuneTech is studying the combination of NT-I7 with Tecentriq, targeting high-risk skin cancers such as melanoma. After completing Phase 1b, the recommended dosage has been determined. The company plans to begin full-scale efficacy evaluation in a Phase 2a clinical trial soon.

Roche has also introduced its own combination therapy, combining Tecentriq with its targeted anticancer drug 'Avastin' for liver cancer. At last year's ASCO meeting, this regimen demonstrated overwhelmingly improved efficacy compared to existing treatments, and it has been listed as the top priority option for first-line treatment of hepatocellular carcinoma in the United States. It is also recommended as a standard therapy in Europe. In Korea, reimbursement for first-line treatment of hepatocellular carcinoma began in May.

This content was produced with the assistance of AI translation services.