Toripalimab + Tifcemalimab for Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+154 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Shanghai Junshi Bioscience Co., Ltd.
Disqualifiers: Autoimmune disease, Immunodeficiency, Active hepatitis, others
Pivotal Trial (Near Approval)
Prior Safety Data
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.
12345What 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.
678910How 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.
13111213Eligibility 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.
+13 more
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
+6 more
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Experimental group BExperimental Treatment2 Interventions
Placebo for tifcemalimab (IV) and toripalimab (240 mg IV)
Group II: Experimental group AExperimental Treatment2 Interventions
Tifcemalimab (200 mg intravenous infusion \[IV\]) and toripalimab (240 mg IV)
Group III: Placebo group CPlacebo Group2 Interventions
Placebos for both tifcemalimab and toripalimab (IV)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
USA029 University of Miami Sylvester Comprehensive Cancer Center 1550 NW 10th Avenue 33173 Miami FL Ikpeazu Chukwuemeka NMiami, FL
Norton Cancer Institute, Downtown, Multidisciplinary ClinicLouisville, KY
Oregon Health and Science UniversityPortland, OR
Karmanos Cancer CenterDetroit, MI
More Trial Locations
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Who Is Running the Clinical Trial?
Shanghai Junshi Bioscience Co., Ltd.Lead Sponsor
References
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]Neoadjuvant and adjuvant immune checkpoint inhibitor treatments for non-small cell lung cancer (NSCLC) patients with resectable disease have presented promising results. This is a phase I study to evaluate the safety and efficacy of neoadjuvant toripalimab in combination with chemotherapy for NSCLC.
Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. [2022]Agents targeting programmed cell death protein 1 (PD-1) have been approved as monotherapy for patients with small cell lung cancer (SCLC). In preclinical models, the combined targeting of PD-1 and delta-like protein 3 resulted in enhanced antitumor activity. Herein, we report results from the expansion arm of study NCT03000257 evaluating the combination of the anti-PD-1 antibody budigalimab and the targeted antibody-drug conjugate rovalpituzumab tesirine (Rova-T) in patients with previously treated SCLC.
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]This trial aimed to analyse the safety, effectiveness and transcriptomic characteristics of neoadjuvant toripalimab plus chemotherapy in II-III non-small-cell lung cancer (NSCLC).
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]Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation.
Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. [2022]Before the availability of immunotherapy, chemotherapy was standard first-line therapy for non-small-cell lung cancer (NSCLC) lacking actionable gene alterations. Preclinical evidence suggests chemotherapy is immunomodulatory, supporting chemotherapy/immunotherapy combinations. Atezolizumab, anti-programmed death ligand-1 (PD-L1) antibody, blocks programmed cell death protein-1 and B7.1 interaction with PD-L1. GP28328 (NCT01633970) assessed atezolizumab with chemotherapy in multiple tumours; we report results for advanced, treatment-naïve NSCLC.
PD-1 inhibitor-based adverse events in solid tumors: A retrospective real-world study. [2022]Background & Aims: Immune checkpoint inhibitors (ICIs) have transformed the landscape of cancer treatment, and ICI-related toxicities (i.e., immune-related adverse events (irAEs) have been reported in many clinical studies. However, the toxicity data of real-world have not been fully assessed. Methods: Patients with histologically confirmed solid tumors who had been treated with PD-1 inhibitors were included in the study. Patient data were collected from electronic medical records, including basic characteristics, data of irAEs, management and outcome. Incidences of irAEs were pooled and compared, and the risk of irAEs was also analyzed. Results: A total of 362 solid tumor patients treated with sintilimab (n = 171), camrelizumab (n = 60), toripalimab (n = 72), and pembrolizumab (n = 59) were included. In total, any grade irAEs, grade 1-2 irAEs, and grade ≥3 irAEs accounted for 47.24%, 38.67% and 8.56% of cases, reapectively. Further, 29.24% of patients discontinued immunotherapy due to irAEs, with pneumonitis being the main reason for discontinuation. By comparing the toxicity profiles between different ICIs, we found that reactive capillary haemangiomas were camrelizumab-specific. Additionally, the frequency of irAEs was association with ICIs type, the pooled incidence (standardized rate) of irAEs related to sintilimab, camrelizumab, toripalimab and pembrolizumab were 55.56% (52.81%), 48.33% (55.55%), 33.33% (29.23%) and 38.98% (38.29%), respectively. Sintilimab and camrelizumab had higher incidences of any grade and grade 1-2 than toripalimab (55.56% vs. 33.33%, p = 0.002; 48.54% vs. 25.00%, p = 0.0001) and pembrolizumab (55.56% vs. 38.98%, p = 0.0028; 48.54% vs. 25.42%, p = 0.002), while the grade ≥3 irAEs of pembrolizumab (13.56%) were approximately 1.63- to 1.93-fold higher than other ICIs, and the standardized grade ≥3 of pembrolizumab was significantly higher than that of sintilimab (13.21% vs. 7.12%, p = 0.026), especially for grade ≥3 pneumonitis. Multivariate analysis found that cumulative cycles of ICI (OR = 1.081; 95% CI: 1.023-1.142; p = 0.006), and lung cancer (OR = 1.765; 95% CI: 1.105-2.820; p = 0.017) were independent risk factors for irAEs. Conclusion: The frequency of irAEs is associated with ICI type. The pooled incidence of irAEs related to sintilimab and pneumonitis caused by pembrolizumab were higher. These data indicate the importance of having different monitoring priorities for different PD-1 inhibitors.
Pneumonitis in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Immunotherapy: Incidence and Risk Factors. [2019]Checkpoint inhibitor pneumonitis (CIP) is an immune-related adverse event that can occur after initiation of anti-programmed death 1/programmed death ligand 1 immune checkpoint inhibitor (ICI) therapy for the treatment of multiple malignancies, including NSCLC. However, the incidence of CIP has not been previously examined in a population that included both trial-enrolled and non-trial-enrolled patients with advanced NSCLC. Furthermore, risk factors and other clinical characteristics associated with CIP severity are not known. In this study, we retrospectively examined clinical characteristics, incidence, and risk factors for CIP in a cohort of 205 patients with NSCLC, all of whom received anti-programmed death 1/programmed death ligand 1 ICIs. Our results demonstrate a higher incidence of CIP (19%) than previously reported in clinical trials (3%-5%). Our data also suggest that tumor histologic type may be a risk factor for CIP development. We observed a wide range of time to onset of CIP (median 82 days), with high morbidity and mortality associated with higher-grade CIP regardless of degree of immunosuppression. Our data provide new insight into the epidemiology and clinical characteristics of CIP. Further studies are needed to increase CIP pharmacovigilance, improve risk stratification, and refine diagnostic algorithms for the diagnosis and management of this potential life-threatening complication of ICI therapy.
Use of a Cancer Registry to Evaluate Patient-Reported Outcomes of Immune Checkpoint Inhibitors. [2021]Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, but few studies have reported on patient-reported outcomes (PROs) outside the context of a clinical trial. The goal of the current study was to assess PROs in participants of a lung cancer registry who had been treated with an ICI. Patients participating in the GO2 Foundation's Lung Cancer Registry who reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab were invited to participate in a survey about their experiences during treatment. Quality of life was evaluated using the Functional Assessment of Cancer Therapy-General (FACT-G). Common symptomatic adverse events were evaluated using an item bank generated for ICIs. Internationally, 226 patients (mean age 61, 75% female) participated. Patients reported worse quality of life at the time of assessment than U.S. population and cancer normative samples. The most common moderate to severe adverse events during ICI treatment were fatigue (41%), aching joints (27%), and aching muscles (20%). Due to toxicity, 25% reported a treatment delay, 11% an emergency room visit, and 9% a hospitalization. This study is among the first to our knowledge to report on PROs of ICIs outside the context of a clinical trial. Results suggest higher rates of adverse events than previously reported in clinical trials.
Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab. [2022]Immune-mediated adverse events (imAEs) may be associated with response to immune checkpoint inhibitors. We assessed the relationship between imAE development and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab (anti-programmed cell death ligand-1 [PD-L1]) alone or in combination with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4).
HLA Expression Correlates to the Risk of Immune Checkpoint Inhibitor-Induced Pneumonitis. [2021]Tumor-infiltrating T cell rescue by programmed cell death receptor-1 (PD-1)/PD-1 ligand-1 (PD-L1) immune checkpoint blockade is a recommended treatment for malignant diseases, including metastatic non-small-cell lung cancer (mNSCLC), malignant melanoma (MM), head and neck, kidney, and urothelial cancer. Monoclonal antibodies (mAbs) against either PD-1 or PD-L1 are active agents for these patients; however, their use may be complicated by unpredictable immune-related adverse events (irAEs), including immune-related pneumonitis (IRP). We carried out a retrospective multi-institutional statistical analysis to investigate clinical and biological parameters correlated with IRP rate on a cohort of 256 patients who received real-world treatment with PD-1/PD-L1 blocking mAbs. An independent radiological review board detected IRP in 29 patients. We did not find statistical IRP rate correlation with gender, tumor type, specific PD-1 or PD-L1 blocking mAbs, radiation therapy, inflammatory profile, or different irAEs. A higher IRP risk was detected only in mNSCLC patients who received metronomic chemotherapy +/- bevacizumab compared with other treatments prior PD-1/PD-L1 blockade. Moreover, we detected a strong correlation among the IRP rate and germinal expression of HLA-B*35 and DRB1*11, alleles associated to autoimmune diseases. Our findings may have relevant implications in predicting the IRP rate in mNSCLC patients receiving PD-1/PD-L1 blockade and need to be validated on a larger patient series.
Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma. [2023]Toripalimab is an immune checkpoint inhibitor (ICI) against programmed death ligand 1 (PD-L1). It has been approved for advanced esophageal squamous cell carcinoma (ESCC) as the first-line treatment due to significantly improved progression-free survival (PFS) and overall survival (OS) in the JUPITER-06 trial.
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]The purpose of this study was to explore the efficacy and safety of toripalimab combined with anlotinib in patients with advanced non-small cell lung cancer (NSCLC) who acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).
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]Approximately 10-25% of patients with small cell lung cancer (SCLC) have brain metastases at the time of diagnosis. Radiotherapy is a common treatment for brain metastases, but the relapse rates are high. Accumulating evidence suggests that immunotherapy may have a better therapeutic effect for brain metastases. Here, we reported a patient with limited-stage SCLC and relapsed brain metastases who achieved sustained intracranial complete response (CR) to programmed cell death-1 (PD-1) inhibitor toripalimab and multikinase inhibitor anlotinib.