Toripalimab + Tifcemalimab for Small Cell Lung Cancer

Recruiting at 154 trial locations

Overseen By Kinga Kovacs, Senior Project Leader

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Disqualifiers: Autoimmune disease, Immunodeficiency, Active hepatitis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

756 Participants Needed

Trial Summary

What is the purpose of this trial?

The Study is a Phase 3, randomized, three-arm, double-blind, placebo-controlled, multi-regional clinical research study to evaluate the safety and efficacy use of toripalimab alone or in combination with tifcemalimab as consolidation therapy in patients with limited-stage small cell lung cancer without disease progression following chemoradiotherapy. Tifcemalimab is a monoclonal antibody against B and T lymphocyte attenuator (BTLA). Toripalimab is a monoclonal antibody against programmed death protein-1 (PD-1). Neither drug is approved for treatment of This combination regimen is investigational in limited stage-small cell lung cancer in any country.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Toripalimab + Tifcemalimab for Small Cell Lung Cancer?

Research shows that toripalimab, when combined with chemotherapy, has shown promising results in treating non-small cell lung cancer (NSCLC). Additionally, drugs targeting PD-1, like toripalimab, have been effective in treating small cell lung cancer (SCLC) in other studies, suggesting potential benefits for this combination. ^{1 2 3 4 5}

What safety data exists for Toripalimab and Tifcemalimab in humans?

Toripalimab, a type of immune checkpoint inhibitor, has been associated with immune-related side effects in cancer patients, such as pneumonitis (lung inflammation) and other adverse events. In a study, 33.33% of patients experienced some form of immune-related adverse event, with 8.56% experiencing severe reactions. These findings highlight the importance of monitoring for side effects during treatment. ^{6 7 8 9 10}

How is the drug Toripalimab + Tifcemalimab unique for treating small cell lung cancer?

Toripalimab is an immune checkpoint inhibitor that has shown promise in treating various cancers by helping the immune system attack cancer cells more effectively. While there is limited direct information on the combination of Toripalimab and Tifcemalimab for small cell lung cancer, Toripalimab has been effective in other cancers and may offer a novel approach by potentially enhancing the immune response against cancer cells. ^{1 3 11 12 13}

Eligibility Criteria

This trial is for adults over 18 with limited-stage small cell lung cancer (LS-SCLC) who've completed chemoradiotherapy without disease progression. They should have responded well to initial treatment, be in good physical condition, and have proper organ function. Women of childbearing age and men with partners of childbearing potential must agree to contraception.

Inclusion Criteria

Voluntarily agree to participate in the study, sign the informed consent form, and agree to comply with all study and follow-up procedures

I've completed a specific chemotherapy and radiation plan and can start the trial within 42 days after my last chemo dose.

I've completed a specific chemotherapy and radiotherapy regimen and can start the trial within 42 days after my last chemo dose.

Exclusion Criteria

My lung cancer is a mix of small cell and non-small cell types.

I have recovered from previous cancer treatment side effects, except for hair loss.

Patients with active autoimmune disease, history of autoimmune disease

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Consolidation Therapy

Participants receive toripalimab alone or in combination with tifcemalimab as consolidation therapy

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 years

Treatment Details

Interventions

• Tifcemalimab
• Toripalimab

Trial Overview The study tests the safety and effectiveness of toripalimab alone or combined with tifcemalimab as additional therapy post-chemoradiotherapy in LS-SCLC patients. Both drugs are monoclonal antibodies; one targets PD-1 and the other BTLA, but neither is yet approved for this cancer type.

Participant Groups

Group I: Experimental group B Experimental Treatment 2 Interventions

Placebo for tifcemalimab (IV) and toripalimab (240 mg IV)

Group II: Experimental group A Experimental Treatment 2 Interventions

Tifcemalimab (200 mg intravenous infusion \[IV\]) and toripalimab (240 mg IV)

Group III: Placebo group C Placebo Group 2 Interventions

Placebos for both tifcemalimab and toripalimab (IV)

Who Is Running the Clinical Trial?

Shanghai Junshi Bioscience Co., Ltd.

Lead Sponsor

Trials

121

Recruited

28,800+

Findings from Research

In a phase I study involving 11 treatment-naive patients with resectable non-small cell lung cancer (NSCLC), the combination of neoadjuvant toripalimab and chemotherapy was found to be tolerable, with 45% of patients experiencing treatment-related adverse events.

The treatment resulted in a high efficacy, with a 91% objective response rate and a 55% rate of pathological complete response, indicating significant potential for this combination therapy in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant toripalimab plus platinum-paclitaxel chemotherapy in stage II-III non-small cell lung cancer: a single-center, single-arm, phase I study in China. Hou, H., Wang, Y., Sun, D., et al.[2023]

The combination of the anti-PD-1 antibody budigalimab and the antibody-drug conjugate Rova-T was found to be tolerated in 31 patients with previously treated small cell lung cancer (SCLC), with common side effects including pleural effusion, fatigue, and cough.

This combination therapy showed an overall response rate of 24.1%, with one complete response and six partial responses, indicating promising efficacy despite the discontinuation of Rova-T's development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Calvo, E., Spira, A., Miguel, M., et al.[2022]

In a trial involving 50 patients with stage II-III non-small-cell lung cancer (NSCLC), neoadjuvant treatment with toripalimab and chemotherapy demonstrated a high objective response rate of 76%, with 100% of patients with resectable disease able to undergo surgery and 55.6% achieving major pathological response (MPR).

The treatment was found to be safe, with manageable adverse events; importantly, baseline expression of CHI3L1 in tumor samples was identified as a potential predictor of therapeutic response and overall survival, highlighting the role of transcriptomic characteristics in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in stage II-III NSCLC (LungMate 002): an open-label, single-arm, phase 2 trial. Zhu, X., Sun, L., Song, N., et al.[2023]

This ongoing phase II clinical trial is evaluating the combination of serplulimab with chemotherapy (etoposide and carboplatin) in 36 patients with transformed small cell lung cancer (T-SCLC) that originated from EGFR-mutant non-small cell lung cancer (NSCLC).

The primary goal of the study is to assess progression-free survival, with secondary goals including overall survival and safety, addressing the urgent need for effective treatments in this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study. Huang, J., Zhang, XH., Cai, Y., et al.[2023]

Atezolizumab combined with chemotherapy showed promising efficacy in treating advanced, treatment-naïve non-small-cell lung cancer (NSCLC), with overall response rates of 36% to 68% across different chemotherapy regimens in a study of 76 patients.

The treatment was generally well tolerated, although common severe side effects included neutropenia and anemia, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. Liu, SV., Camidge, DR., Gettinger, SN., et al.[2022]

In a study of 362 patients with solid tumors treated with PD-1 inhibitors, the overall incidence of immune-related adverse events (irAEs) was 47.24%, with 29.24% of patients discontinuing treatment due to these toxicities, primarily pneumonitis.

Different PD-1 inhibitors showed varying toxicity profiles, with sintilimab and camrelizumab having higher rates of any grade and grade 1-2 irAEs compared to toripalimab and pembrolizumab, which had a notably higher incidence of grade ≥3 irAEs, particularly pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 inhibitor-based adverse events in solid tumors: A retrospective real-world study. Huang, G., Liu, S., Dong, J., et al.[2022]

In a study of 205 patients with advanced non-small cell lung cancer (NSCLC) receiving anti-PD-1/PD-L1 therapy, the incidence of checkpoint inhibitor pneumonitis (CIP) was found to be 19%, significantly higher than the 3%-5% reported in clinical trials.

The study identified tumor histologic type as a potential risk factor for developing CIP, with a median onset time of 82 days and severe outcomes associated with higher-grade CIP, highlighting the need for improved monitoring and management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pneumonitis in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Immunotherapy: Incidence and Risk Factors. Suresh, K., Voong, KR., Shankar, B., et al.[2019]

In a study of 226 lung cancer patients treated with immune checkpoint inhibitors (ICIs), participants reported a lower quality of life compared to both the general U.S. population and cancer normative samples, indicating significant treatment impact.

The most common adverse events included fatigue (41%), joint pain (27%), and muscle pain (20%), with 25% of patients experiencing treatment delays due to toxicity, highlighting the need for careful monitoring and management of side effects in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a Cancer Registry to Evaluate Patient-Reported Outcomes of Immune Checkpoint Inhibitors. Jim, HSL., Eisel, SL., Hoogland, AI., et al.[2021]

Patients with metastatic non-small-cell lung cancer who developed immune-mediated adverse events (imAEs) while treated with durvalumab showed significantly improved overall survival compared to those without imAEs, indicating a potential link between imAE development and treatment efficacy.

A predictive model was created using machine learning to identify patients at higher risk of developing imAEs, which could help tailor treatment strategies and enhance patient outcomes in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab. Dey, A., Austin, M., Kluger, HM., et al.[2022]

In a study of 256 patients treated with PD-1/PD-L1 blocking monoclonal antibodies, immune-related pneumonitis (IRP) was observed in 29 patients, indicating a notable risk of this adverse event in real-world settings.

The research found that the risk of IRP was particularly higher in patients with metastatic non-small-cell lung cancer (mNSCLC) who had received metronomic chemotherapy, suggesting that treatment history may influence the likelihood of developing IRP during PD-1/PD-L1 blockade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA Expression Correlates to the Risk of Immune Checkpoint Inhibitor-Induced Pneumonitis. Correale, P., Saladino, RE., Giannarelli, D., et al.[2021]

Toripalimab, an immune checkpoint inhibitor, significantly improves progression-free survival and overall survival in advanced esophageal squamous cell carcinoma when combined with chemotherapy, as shown in the JUPITER-06 trial.

However, from a cost-effectiveness perspective in China, adding toripalimab to chemotherapy is not considered cost-effective unless its price is reduced by over 40%, as the incremental cost-effectiveness ratio exceeds the country's willingness-to-pay threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma. Xu, K., Wu, H., Zhou, C., et al.[2023]

In a study of 19 patients with advanced non-small cell lung cancer resistant to EGFR-TKIs, the combination of toripalimab and anlotinib showed an objective response rate of 0%, indicating that this treatment did not effectively shrink tumors in this group.

The median progression-free survival was 2.1 months, and while the treatment was generally tolerable with 11% experiencing severe side effects, patients without detectable EGFR mutations and those with high levels of soluble PD-L1 may have a better response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of chemo-free therapy in epidermal growth factor receptor tyrosine kinase inhibitor-resistant advanced non-small cell lung cancer: A single-arm, phase II study. Zhang, S., Yang, L., Yang, Y., et al.[2023]

A 59-year-old female patient with limited-stage small cell lung cancer (SCLC) and relapsed brain metastases achieved a sustained complete response (CR) after treatment with the PD-1 inhibitor toripalimab combined with the multikinase inhibitor anlotinib, following initial therapies.

This case highlights the potential of toripalimab and anlotinib as an effective treatment option for brain metastases in SCLC, showing no serious adverse reactions and sustained CR of both brain lesions and the primary lung tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial complete response to toripalimab and anlotinib in a patient with recurrent brain metastases of small cell lung cancer after failure of second-line maintenance therapy: a case report. Huang, F., Tang, J., Lou, J., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant toripalimab plus platinum-paclitaxel chemotherapy in stage II-III non-small cell lung cancer: a single-center, single-arm, phase I study in China. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in stage II-III NSCLC (LungMate 002): an open-label, single-arm, phase 2 trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

PD-1 inhibitor-based adverse events in solid tumors: A retrospective real-world study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Pneumonitis in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Immunotherapy: Incidence and Risk Factors. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Use of a Cancer Registry to Evaluate Patient-Reported Outcomes of Immune Checkpoint Inhibitors. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

HLA Expression Correlates to the Risk of Immune Checkpoint Inhibitor-Induced Pneumonitis. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

The efficacy and safety of chemo-free therapy in epidermal growth factor receptor tyrosine kinase inhibitor-resistant advanced non-small cell lung cancer: A single-arm, phase II study. [2023]

13. China pubmed.ncbi.nlm.nih.gov

Intracranial complete response to toripalimab and anlotinib in a patient with recurrent brain metastases of small cell lung cancer after failure of second-line maintenance therapy: a case report. [2022]