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Envafolimab plus lenvatinib and paclitaxel shows activity in advanced gastric cancer after first-line progressionNew Drug Combo Gives Hope for Late-Stage Stomach Cancer

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Key Takeaway
Consider this combination as a potential option in MSS advanced gastric cancer after first-line progression, noting the small, non-randomized trial.

This was a prospective, phase II, multi-cohort, single-center, open-label trial in 30 patients with HER2-negative, microsatellite stable (MSS) advanced gastric/gastroesophageal junction adenocarcinoma who had progressed after first-line treatment. The intervention was envafolimab (200 mg subcutaneously on days 1 and 15, every 4 weeks) combined with lenvatinib and albumin-bound paclitaxel (100 mg/m² intravenously on days 1, 8, and 15, every 4 weeks, up to 6 cycles). There was no reported comparator.

In Group A, the objective response rate (ORR) was 60.0%, the disease control rate (DCR) was 100.0%, median progression-free survival (mPFS) was 8.2 months (95% CI 6.1-10.4), and median overall survival (mOS) was 14.8 months (95% CI 7.4-22.2). In Group B, the ORR was 46.7%, DCR was 100.0%, mPFS was 5.9 months (95% CI 3.8-8.1), and mOS was 11.5 months (95% CI 3.1-19.9). There was no statistically significant difference in PFS (P = 0.629) or OS (P = 0.873) between Group A and Group B.

The overall incidence of adverse events of any grade was 100%. Follow-up was median 17.0 months (IQR: 8.0-18.8) in Group A and 9.0 months (IQR: 6.1-16.2) in Group B. Key limitations include the small sample size, lack of a comparator, and non-randomized design. Practice relevance was not reported. These results are preliminary and require validation in larger, randomized studies.

Imagine a patient who has already tried every standard treatment available. Their cancer has returned, and options are running low. Now, a new combination therapy offers a fresh chance at control.

Stomach cancer, or gastric cancer, is often found late. By the time it spreads, it is hard to treat. Many patients receive chemotherapy first. But eventually, the cancer grows back. Doctors call this progression.

Current options for later stages are limited. Patients need new tools. This study looks at a specific new drug called envafolimab. It works with two other medicines: lenvatinib and paclitaxel.

The surprising shift

For years, doctors relied on a specific type of immune checkpoint inhibitor. These drugs help the body fight cancer. But some patients stop responding to them. They need a different approach.

This trial tested a new mix. It included patients who had never used these immune drugs before. It also included those who had used them but saw their cancer grow again. The results were encouraging for both groups.

What scientists didn't expect

Cancer cells often hide from the immune system. Think of it like a lock and key. The immune system holds the key, but the cancer changes the lock. New drugs try to force the key back in.

Envafolimab acts like a helper. It boosts the immune system's ability to find and attack cancer cells. When combined with chemotherapy and lenvatinib, the attack becomes stronger. The goal is to stop the cancer from spreading for longer.

The study snapshot

Thirty patients joined this research. They all had advanced stomach cancer that had come back. Half had not used immune drugs before. The other half had used them and failed.

Everyone got the new drug mix. They received injections every four weeks. Treatment continued until the cancer grew or side effects became too strong. Researchers watched closely for two years.

The most important result was how well the cancer shrank. In the group that had never used immune drugs, sixty percent of patients saw their tumors shrink. This is a high number for late-stage disease.

In the group that had used immune drugs before, forty-seven percent saw shrinkage. Even though the numbers were lower, the treatment still worked well. In both groups, the cancer stopped growing in every single patient for some time.

This doesn't mean this treatment is available yet.

The study showed that patients lived longer than expected in similar past trials. The average time without cancer growth was over eight months for the first group. For the second group, it was nearly six months. These times are significant for people facing a difficult diagnosis.

Doctors see many patients with no good options left. This new mix gives them a new path. It fits into the bigger picture of personalized medicine. Not every patient responds to the same drug. This trial shows flexibility in how we treat cancer.

If you or a loved one has stomach cancer, talk to your doctor. Ask if this new combination fits your situation. It is currently in a research phase. It is not yet a standard option everywhere.

Do not stop current treatments without medical advice. This news is hopeful, but it is not a magic fix. It is a step forward in a long journey.

This study was small. Only thirty people took part. It was done at one medical center. Results from a small group might not match results from a larger group. Also, the drug is new. Long-term safety data is still being collected.

More research is needed before this becomes a standard treatment. Large studies will follow to confirm these results. Regulators will review the safety and effectiveness data. If approved, it could help many more patients. Until then, it remains a promising option for clinical trials.

Study Details

Study typePhase2
Sample sizen = 30
EvidenceLevel 3
PublishedApr 2026
View Original Abstract ↓
BACKGROUND: This single-center, open-label, exploratory trial aimed to investigate the efficacy and safety of envafolimab combined with lenvatinib and chemotherapy in previous treated advanced G/GEJ adenocarcinoma. METHODS: Eligible patients with HER2-negative, microsatellite stable (MSS) advanced G/GEJ adenocarcinoma who had progressed after first-line treatment were enrolled in this phase II trial. Patients without previously receiving PD-1/PD-L1 inhibitors were enrolled in Group A, and those who progressed on the first-line PD-1 inhibitors were included in Group B. Patients in both groups received envafolimab (200 mg, subcutaneous injection (sc), days 1 and 15, Q4W) combined with lenvatinib and albumin-bound paclitaxel (100 mg/m, IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or refusal of continuation. The primary endpoint was objective response rate (ORR). RESULTS: A total of 30 patients were included for safety and efficacy analysis. As of data cutoff (Sep 14, 2024), the median follow-up was 17.0 months (IQR: 8.0-18.8) in Group A. The ORR was 60.0%, and the DCR was 100.0%. The mPFS was 8.2 months (95% CI 6.1-10.4) with mOS of 14.8 months (95% CI 7.4-22.2). With a median follow-up of 9.0 months (IQR: 6.1-16.2) in Group B, the ORR was 46.7%, and the DCR was 100.0%. The mPFS was 5.9 months (95% CI 3.8-8.1), and the mOS was 11.5 months (95% CI 3.1-19.9). The overall incidence of adverse events (AEs) of any grade was 100%. While Group A showed numerically better outcomes than Group B, there was no statistically significant difference in PFS (P = 0.629) or OS (P = 0.873) between the two groups. CONCLUSIONS: Second-line envafolimab-based combination therapy demonstrated promising effects in previously treated advanced GC, particularly in those who have not previously received ICIs.
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