The chemotherapy cisplatin has been a staple in cancer treatment since the 1980s. However, not all cancer patients respond to the drug, and the side effects are quite severe. Chosa Oncology is looking to tackle both of these drawbacks with its iCIP concept. BioStock has taken a closer look at this revolutionary cancer treatment and how the company is working to take it to the next level.

The platinum-based substance cisplatin was first discovered in 1845 and has been used for medical purposes since the late 1970s. It entered the oncology space during the 1980s, providing a revolutionary breakthrough especially for testicular cancer patients. Before the introduction of cisplatin, the survival rate among testicular cancer patients was approximately 10 per cent. Today, the survival rate sits at approximately 85 per cent.

The drug is on the World Health Organization’s list of essential medications and is currently used in the treatment of several cancer types. Some examples, apart from testicular cancer, are breast cancer, cancer of the uterus and cervical cancer, lung cancer, head & neck cancer and brain cancer.

Kills the fastest growing cells

Cisplatin is given via infusion and works by interfering with DNA replication. This kills the fastest growing cells in the body, making cancer cells perfect targets. The downside is of course, like with any chemotherapy, that cisplatin is associated with serious side effects. Common side effects include hearing problems, kidney damage, and vomiting. The patient may also experience nausea, numbness and difficulty walking.

Through the years, drug developers have put a lot of effort to try to come up with better versions of cisplatin, especially with the toxicity in mind. While five other platinum drugs based on its structure have been developed, cisplatin itself has never been replaced. In 2022, the platinum-based drug market was estimated at 1.5 billion USD, and by 2030 it is expected to reach approximately 1.9 billion USD.

Not all patients respond to cisplatin

Another thing to consider when using cisplatin is the response rate, which differs between various cancers. Whereas the cisplatin response rate is high in testicular cancer, it is only between 20 and 40 per cent for lung cancer patients. Looking at the overall breast cancer population, the response rate is only between 10 and 20 per cent.

There are different strategies aimed at overcoming cisplatin resistance, with one being combining it with other drugs. One example is the cisplatin/paclitaxel combination, which has been shown to increase response rates and survival in patients suffering from uterine cancer.

DRP targets the cisplatin responders

Still, the response uncertainty is high in many cancer indications, which is a problem considering the drug´s severe side effects. This uncertainty is at the very core of the development for Copenhagen-based Chosa Oncology. The biotech’s proprietary Drug Response Predictor (DRP) algorithm uses the expression state of 205 tumour genes to predict whether or not the use of cisplatin will work for the specific patient.

This has the potential to be a very useful tool – if a patient receives the wrong medication, the tumour continues to grow and valuable time is lost, while unnecessarily exposing the patient to serious side effects.

Chosa Oncology aims for better safety and efficacy profile

For the group of patients that actually benefit from the use of cisplatin, Chosa has developed a new formulation of the drug. LiPlaCis, as it is called, is designed to specifically target the tumour site. This spares the healthy cells in the body, and the company has also reported signs that the new formulation may even be more effective than the original.

Initial focus set on breast cancer

DRP and LiPlaCis together make up the iCIP-concept, and Chosa Oncology’s main focus with the concept right now is late-stage metastatic breast cancer. Breast cancer is one of the most common cancer types in women, with more than 2 million diagnosed each year. In this late stage of the disease, the patient is usually treated with hormone therapy, immunotherapy, chemo, targeted therapy or combinations of these. Even if other platinum type chemotherapies are used, cisplatin is still considered the one that brings the most benefit.

With LiPlaCis, Chosa hopes to provide breast cancer patients with a less toxic version of cisplatin. But perhaps more importantly, using the DRP physicians will be able to use either cisplatin or the LiPlaCis formulation only on patients that will actually respond.

Potential in earlier stages as well

Further down the road, the company also sees potential in introducing LiPlaCis as a neoadjuvant treatment in cisplatin-responding breast cancer patients. Today, the chemotherapy doxorubicin is used to make the tumour as small as possible when preparing for surgery.

Combining doxorubicin with cisplatin would make the so called downstaging of the tumour more effective, increasing the odds that the patient can keep the breast. However, this is not done today due to the high toxicity. Chosa believes that LiPlaCis would be a possible solution to this problem.

Phase IIb results presented at ASCO – the largest cancer conference in the world

At this year’s ASCO conference, held on June 2 – 6, Chosa presented results from its recently completed phase IIb study. 37 previously heavily treated patients with metastatic breast cancer were diagnosed using the DRP tool. That group of heavily treated patients is particularly difficult to help. The results showed that the 16 patients who got high DRP scores were also the ones that were helped by LiPlaCis, with a 2.5 times longer median progression free survival. According to the company, these results show the DRP test can find a large fraction of breast cancer patients that benefit from LiPlaCis. Learn more about the results here.

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