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Combining therapies: MASCT-I, TKI and ICI in a therapeutic approach to treating sarcomas

by | Apr 25, 2024 | Clinical Trials, Research | 0 comments

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Bone and soft tissue sarcomas are known to have poor treatment response and outcomes. The standard treatment of surgery alongside chemotherapy and radiotherapy often does not resolve the disease. At least 40% people who have these treatments will develop cancer that has grown back (recurrent) or spread to other parts of the body (metastatic). Treatment for such sarcomas is a challenge for medical professionals.

TKI therapy (tyrosine kinase inhibitors) is a type of cancer treatment, and it works by blocking the action of tyrosine kinase enzymes within cells. This can help stop the growth of cancer cells. In sarcomas, TKI therapy and chemotherapy have only a moderate response rate.

Innovative treatment for these cancers is needed. This trial looks at combining several types of treatments in patients with a range of bone and soft tissue sarcomas. This includes osteosarcoma (OS). As far as the researchers know, this is a new combination of treatments which could lead to new therapeutic approaches to treating OS.

The treatment used in this study is known as MASCT-I combined with an immune checkpoint inhibitor drug and a TKI inhibitor treatment. Checkpoint inhibitors (CI) activate the body’s immune system to kill cancer. They achieve this by targeting T cells, a type of immune cell. CIs are part of a wider group of drugs that affect the immune system known as immunotherapies.

There were 19 people in this trial. 6 of these people had OS. For the purpose of this blog post, we will look at the OS outcomes.

What is MASCT-I Therapy?

Multi-antigen stimulated cell therapy-I (MASCT-I) is an innovative approach in cancer treatment. It combines multiple antigen-loaded dendritic cell (DC) vaccines with the adoptive transfer of anti-tumor effector T-cells. Let’s break it down: 1. Dendritic Cell Vaccines (DC Vaccines): These are antigen-presenting cells that play a crucial role in activating the immune response. In MASCT-I, DCs are loaded with multiple tumor-associated antigens. 2. Anti-Tumor Effector T-Cells: These are T-cells specifically designed to target and destroy cancer cells. In MASCT-I, these T-cells are infused after the DC vaccinations. 3. Treatment Process: MASCT-I involves a sequential approach. First, patients receive three subcutaneous injections of DCs. Then, 18–27 days later, they receive three infusions of active T-cells. The timing and intervals vary based on the treatment schedule. 4. Combination Therapy: MASCT-I is often combined with other treatments. For instance, in the pilot study, patients received MASCT-I along with camrelizumab (an immune checkpoint inhibitor targeting PD-1) and apatinib (a tyrosine kinase inhibitor targeting VEGFR2).

There were two treatment groups in this study. Both groups received the same treatment but on a different schedule. This was so the researchers could see if the timings of giving the treatments made any difference to how the drugs performed on sarcomas.

Group 1: 28 days between each DC shots and then T cell infusions

Group 2: 7 days between DC dose one and dose two and then 28 days between each DC shot and then T cell infusion.

All patients also received a drug called camrelizumab (an immune checkpoint inhibitor) every 3 weeks. This was administered into the body via a drip. They also received a TKI inhibitor drug called apatinib every day in tablet form.

What were the results?

Trials looking at effectiveness of cancer treatments often use the following terms in their outcomes:

ORR – overall response rate. This is the proportion of patients with a specified reduction in tumour size over a predefined amount of time. ORR is used as a marker for drug approval.

DCR – Disease control rate. This is the percentage of patients with metastatic cancer who achieve a complete, partial, or stable response to treatment.

PFS – Progression free survival. How long a patient lives with cancer without it getting worse or spreading (metastasising). This can be a length of time or a percentage of patients who remain stable in a predefined time period.

In the 6 OS patients in this trial:

  • ORR was 30.8%. This means that 30.8% of OS patients resulted in their tumour size shrinking over the predefined amount of time.
  • DCR was 50%. This means that 3 out of 6 patients with OS achieved a response to treatment.
  • PFS was 5.7 months. This means that for an average of 5.7 months after treatment, osteosarcoma patients were stable in their cancer progression.

Between groups 1 and 2 being treated, the following differences were noted:

  1. Group 1 patients had a higher number of treatment–related adverse events (such as pneumonia caused by the treatment).  This could be explained by the length of treatment time. In Group 1, the length of treatment time was longer than the time in Group 2, so there are more chances of these adverse events happening.
  2. Group 2’s treatment schedule was linked to better clinical outcomes than Group 1. For example, for all patients the DCR was 90% in Group 2 versus 44.4% in Group 1.

What can we learn from this study?

The results indicate that Group 2’s treatment regime is more clinically effective. The researchers suggest that further clinical trials are done to progress the MASCT-1 with TKI and ICI treatment plan to help bone and soft tissue sarcoma patients.

You can read more about this trial at ClinicalTrials.gov

References:

  1. Zhou, Y., Li, M., Zhang, B. et al. A pilot study of multi-antigen stimulated cell therapy-I plus camrelizumab and apatinib in patients with advanced bone and soft-tissue sarcomas. BMC Med 21, 470 (2023). https://doi.org/10.1186/s12916-023-03132-x

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