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TIFCEMALIMAB

Tifcemalimab is an investigational immunotherapy drug being studied in clinical trials for small cell lung cancer (SCLC). Current trials are testing tifcemalimab either together with another immunotherapy drug called toripalimab or as part of a combination that also includes chemotherapy and low-dose radiotherapy. These studies are mainly looking at how safe the treatment is and whether it helps people live longer or keeps the cancer from growing for longer.

Table of Contents

What is tifcemalimab (JS004)?

Tifcemalimab (also described as JS004) is a monoclonal antibody drug designed to target BTLA (B and T lymphocyte attenuator), which is a molecule involved in reducing immune activity (sometimes explained as an immune “brake”). In the provided trials, it is being studied as an immunotherapy approach for small cell lung cancer, often paired with another immunotherapy drug, toripalimab.[1][2] Toripalimab is also a monoclonal antibody, but it targets PD-1 (programmed death protein-1), another immune “brake.” The trials are exploring whether blocking these immune checkpoints (BTLA and PD-1) can improve cancer control in small cell lung cancer when used alone or together, depending on the study design.[1]

What cancers are being studied?

The provided clinical trial records study tifcemalimab in Small Cell Lung Cancer (SCLC), which is a fast-growing type of lung cancer. Two stages/settings are included in these trials: Limited-stage Small Cell Lung Cancer (LS-SCLC) and Extensive-stage Small-cell Lung Cancer (ES-SCLC).[1][2]
  • LS-SCLC: In one phase 3 trial, patients have limited-stage disease and have already received chemoradiotherapy (CRT) (chemotherapy plus radiation). Importantly, the study focuses on patients who have no disease progression after CRT, and then tests immunotherapy as consolidation therapy (extra treatment after the first main treatment to help keep cancer controlled).[1]
  • ES-SCLC: In one exploratory trial, tifcemalimab is tested in the first-line setting (the first treatment given) for extensive-stage disease, together with chemotherapy, toripalimab, and low-dose radiotherapy.[2]

How tifcemalimab is given in these trials

In the provided studies, tifcemalimab is given as an intravenous infusion (IV), meaning the medicine is delivered into a vein. The dosing schedule in both trials is every 3 weeks (often written as q3w).[1][2]
  • In the phase 3 LS-SCLC consolidation trial, tifcemalimab is listed as 200 mg IV once every 3 weeks, and toripalimab is 240 mg IV once every 3 weeks in the combination arm.[1]
  • In the ES-SCLC exploratory study, tifcemalimab is tested at 100 mg or 200 mg every 3 weeks together with toripalimab 240 mg every 3 weeks, and treatment continues until disease progression (cancer clearly worsens) or intolerable toxicity (side effects are too severe to continue).[2]

Phase 3 consolidation trial in limited-stage SCLC (NCT06095583)

This study is a Phase 3, randomized, double-blind, placebo-controlled, multi-regional clinical trial. These terms mean: Phase 3 is a large later-stage trial, randomized means assigned by chance, double-blind means the treatment is masked (hidden) to reduce bias, placebo-controlled means some participants receive inactive infusions for comparison, and multi-regional means it is run across multiple regions.[1] The trial tests consolidation therapy in patients with LS-SCLC who do not have disease progression after chemoradiotherapy (CRT). Consolidation therapy here means additional treatment after CRT to try to keep the cancer controlled for longer.[1]
  • Arm A (experimental): tifcemalimab 200 mg IV + toripalimab 240 mg IV every 3 weeks.[1]
  • Arm B (experimental): toripalimab 240 mg IV every 3 weeks + placebo for tifcemalimab.[1]
  • Arm C (placebo comparator): placebo for both drugs (placebos for tifcemalimab and toripalimab) every 3 weeks.[1]
The record also states that tifcemalimab is a monoclonal antibody against BTLA and toripalimab is a monoclonal antibody against PD-1, and that this combination regimen is investigational (not approved as standard treatment) in limited-stage SCLC in any country according to the trial description.[1]

Exploratory first-line trial in extensive-stage SCLC (NCT06732258)

This study is a single-center, single-arm, exploratory clinical study in ES-SCLC (extensive-stage disease). Single-arm means everyone receives the same treatment (there is no placebo/control group in this study). The aim is to evaluate tolerability and safety and determine the RP2D (recommended Phase 2 dose).[2] The trial uses a 3 + 3 dose escalation design, which is a method used in early trials to find a dose that people can tolerate. A key safety window is the first 21 days after the first dose, when dose-limiting toxicities (DLTs) are monitored. DLTs are side effects serious enough to limit how much drug can be safely given.[2] The treatment approach combines four components: low-dose radiotherapy, standard chemotherapy drugs, toripalimab, and tifcemalimab. This is designed to study safety and early signs of cancer response in the first-line setting for ES-SCLC.[2]
  • Low-dose radiotherapy: total dose 15 Gy delivered in 5 fractions (15 Gy/5F), starting on Cycle 1 Day 1. Gy is a unit of radiation dose, and fractions are separate treatment sessions.[2]
  • Chemotherapy: cisplatin 75 mg/m² every 3 weeks or carboplatin at AUC = 5 every 3 weeks, plus etoposide 100 mg/m² on days 1, 2, and 3 every 3 weeks for 4–6 cycles. These are standard chemotherapy drugs used to kill or slow cancer cell growth.[2]
  • Toripalimab: 240 mg every 3 weeks until disease progression or intolerable toxicity.[2]
  • Tifcemalimab: 100 mg or 200 mg every 3 weeks until disease progression or intolerable toxicity (the dose levels support the dose-escalation goal and RP2D selection).[2]

What outcomes (endpoints) the trials measure

Clinical trials use outcomes (also called endpoints) to measure whether a treatment is helping and how safe it is. In these tifcemalimab trials, outcomes include survival, time without cancer worsening, and tumor response categories.[1][2]
  • Overall survival (OS): how long participants live. In the phase 3 LS-SCLC trial, OS is a primary outcome used to compare Arm A versus placebo and Arm B versus placebo.[1]
  • Progression-free survival (PFS): how long participants live without the cancer getting worse. In the LS-SCLC trial, PFS is assessed by a Blinded Independent Review Committee (BIRC) to reduce bias, and there are also investigator-assessed PFS secondary outcomes. In the ES-SCLC trial, PFS is also measured as time from enrollment to progression or death.[1][2]
  • Objective response rate (ORR): the proportion of participants who have a measurable tumor shrinkage, defined as complete response (CR) or partial response (PR). ORR is included as a secondary outcome in both trials (listed in LS-SCLC and defined clearly in ES-SCLC).[1][2]
  • Disease control rate (DCR): the proportion of participants who have CR, PR, or stable disease (SD), meaning the cancer shrinks or does not grow for a time. DCR is listed as a secondary outcome in the LS-SCLC trial and defined in the ES-SCLC trial.[1][2]
  • Duration of response (DoR/DOR): how long a response lasts from first documented response until progression or death. DoR is included in both trials (and defined in the ES-SCLC study).[1][2]
  • In the LS-SCLC phase 3 trial, 1-year and 2-year OS rates are also included as secondary outcomes for both the combination comparison and the toripalimab-only comparison versus placebo.[1]

How safety is monitored in these trials

Safety monitoring in these studies focuses on side effects (called adverse events) and laboratory test changes, and in the ES-SCLC exploratory study it also focuses on early serious side effects called dose-limiting toxicities (DLTs).[1][2]
  • In the phase 3 LS-SCLC consolidation trial, safety is evaluated by the incidence (percentage of participants affected) of treatment-related adverse events graded using CTCAE v5.0 (a standard system to rate side effect severity) and by abnormal laboratory parameters, comparing combination therapy versus placebo and toripalimab versus placebo.[1]
  • In the ES-SCLC exploratory study, the primary safety outcome is the number of participants with DLTs during the first 21 days after the first dose. This period helps researchers decide which dose levels are tolerable and supports choosing the RP2D for future studies.[2]
Topic What the trials show (from provided trial records)
Drug being studied Tifcemalimab (JS004), a monoclonal antibody targeting BTLA
Main cancer types studied Limited-stage SCLC (after chemoradiotherapy, no progression) and extensive-stage SCLC (first-line)
Key combinations Tifcemalimab + toripalimab; and in ES-SCLC also combined with chemotherapy (cisplatin or carboplatin + etoposide) and low-dose radiotherapy
How it is given IV infusion every 3 weeks: tifcemalimab 200 mg (LS-SCLC) or 100/200 mg (ES-SCLC); toripalimab 240 mg
Main goals (efficacy) Overall survival (OS) and progression-free survival (PFS), plus ORR, DCR, and DoR
Main goals (safety) Adverse events (graded by CTCAE v5.0) and dose-limiting toxicities (DLTs) in early safety monitoring
Study designs in the provided data Phase 3 randomized double-blind placebo-controlled (LS-SCLC); single-arm exploratory 3+3 dose escalation (ES-SCLC)
Approval status mentioned Combination regimen described as investigational; not approved for LS-SCLC in any country (per trial record)

FAQ

  • What is tifcemalimab and how does it work in these trials? Tifcemalimab is a monoclonal antibody (a lab-made protein designed to target a specific molecule) that blocks BTLA (B and T lymphocyte attenuator). BTLA is a type of “immune brake” that can reduce immune activity. In these trials, tifcemalimab is being studied to see if blocking BTLA can help the immune system fight small cell lung cancer, often in combination with toripalimab, another immunotherapy drug that targets PD-1 (another immune brake).
  • Which types of small cell lung cancer are being studied with tifcemalimab? Two main settings are being studied: limited-stage SCLC (LS-SCLC) after chemoradiotherapy when the cancer has not progressed, and extensive-stage SCLC (ES-SCLC) as first-line treatment (the first treatment given for the disease).
  • How is tifcemalimab given in these clinical trials? In the LS-SCLC phase 3 trial, tifcemalimab is given as an intravenous infusion (IV) at 200 mg once every 3 weeks, together with toripalimab 240 mg IV every 3 weeks. In the ES-SCLC exploratory study, tifcemalimab is given at 100 mg or 200 mg every 3 weeks along with toripalimab, chemotherapy, and low-dose radiotherapy.
  • What are the main outcomes researchers are measuring? In the phase 3 LS-SCLC trial, key outcomes include overall survival (OS, how long people live) and progression-free survival (PFS, how long people live without the cancer getting worse), including PFS assessed by a Blinded Independent Review Committee (BIRC). In the ES-SCLC exploratory study, the main focus is safety using dose-limiting toxicities (DLTs) during the first 21 days, and it also measures tumor response outcomes like ORR (objective response rate), DCR (disease control rate), DoR (duration of response), PFS, and OS.
  • Is tifcemalimab approved for small cell lung cancer? No. In the LS-SCLC phase 3 study description, it states that neither tifcemalimab nor toripalimab is approved for treatment in this limited-stage SCLC combination regimen, and the regimen is investigational.

Ongoing Clinical Trials on TIFCEMALIMAB

  • Study on Toripalimab and Tifcemalimab for Patients with Limited-Stage Small Cell Lung Cancer After Chemoradiotherapy

    Recruiting

    1 1
    Investigated drugs:
    Belgium France Germany Italy The Netherlands Poland +2

Glossary

  • Tifcemalimab (JS004): An investigational monoclonal antibody drug that targets BTLA, a molecule that can reduce immune system activity. It is being studied for small cell lung cancer in combination approaches.
  • Toripalimab: An investigational monoclonal antibody drug that targets PD-1, a checkpoint on immune cells. Blocking PD-1 can help immune cells attack cancer.
  • Monoclonal antibody: A lab-made protein designed to attach to one specific target in the body. In cancer, monoclonal antibodies may help the immune system recognize or attack cancer cells.
  • BTLA (B and T lymphocyte attenuator): A protein involved in lowering immune activity (an immune “brake”). Blocking BTLA is being studied to see if it strengthens anti-cancer immune responses.
  • PD-1 (programmed death protein-1): A checkpoint protein on immune cells that acts like an off-switch. Some cancers use this pathway to hide from the immune system. PD-1 inhibitors aim to remove this brake.
  • Small Cell Lung Cancer (SCLC): A fast-growing type of lung cancer. The trials here study both limited-stage and extensive-stage SCLC.
  • Limited-stage SCLC (LS-SCLC): SCLC that is limited to one side of the chest and may be treatable with combined chemotherapy and radiation. One trial studies consolidation treatment after chemoradiotherapy when the disease has not progressed.
  • Extensive-stage SCLC (ES-SCLC): SCLC that has spread more widely. One trial studies a first-line combination including immunotherapy, chemotherapy, and low-dose radiotherapy.
  • Chemoradiotherapy (CRT): Treatment that combines chemotherapy (anti-cancer drugs) and radiotherapy (radiation treatment). In LS-SCLC, a trial studies immunotherapy after CRT if the cancer has not worsened.
  • Consolidation therapy: Extra treatment given after the initial therapy (such as chemoradiotherapy) to try to keep cancer under control longer and reduce the chance of it coming back or growing.
  • Intravenous infusion (IV): A method of giving medication directly into a vein, often over a set time.
  • Randomized: A study method where participants are assigned by chance to different treatment groups to reduce bias.
  • Double-blind: A study design where participants and study staff (and/or outcome assessors) do not know which treatment the participant is receiving, helping reduce bias.
  • Placebo-controlled: A study design where one group receives an inactive treatment (placebo) so researchers can compare results fairly.
  • Multi-regional: A trial carried out in more than one region/country, which can help understand how treatments perform across different populations.
  • Overall Survival (OS): The time from a defined starting point in a study to death from any cause. It is a common way to measure whether a treatment helps people live longer.
  • Progression-Free Survival (PFS): The time during and after treatment that a person lives without the cancer getting worse.
  • Blinded Independent Review Committee (BIRC): A group of independent experts who review imaging and other data to judge cancer progression, without knowing which treatment the patient received.
  • Objective Response Rate (ORR): The percentage of patients whose cancer shrinks by a defined amount, including complete response (CR) or partial response (PR).
  • Disease Control Rate (DCR): The percentage of patients who achieve complete response (CR), partial response (PR), or stable disease (SD), meaning the cancer shrinks or does not worsen for a period.
  • Duration of Response (DoR/DOR): How long the cancer remains improved (responding) before it gets worse again or the patient dies.
  • Dose-limiting toxicity (DLT): A side effect serious enough to limit how much of a treatment can be safely given. In one trial, DLTs are monitored during the first 21 days after the first dose.
  • RP2D (recommended Phase 2 dose): The dose chosen for later studies based on safety and tolerability findings, often from early-phase trials using dose escalation.
  • 3 + 3 dose escalation design: A common early-trial method to find a safe dose. Small groups (often 3 people at a time) receive a dose, and the dose may be increased depending on side effects observed.
  • Low-dose radiotherapy (LDRT): Radiation treatment given at a lower total dose than standard regimens. In one trial, LDRT is 15 Gy given in 5 fractions (15 Gy/5F).
  • Gy (Gray): A unit used to measure the amount of radiation dose delivered.
  • Fraction (F): One session of radiotherapy. For example, 15 Gy/5F means the total radiation dose is divided into 5 treatment sessions.
  • Chemotherapy: Cancer treatment using drugs that kill or slow the growth of cancer cells. In one ES-SCLC trial, chemotherapy includes cisplatin or carboplatin plus etoposide.
  • Cisplatin: A chemotherapy drug used in some lung cancer regimens. In the ES-SCLC trial, it can be given at 75 mg/m² every 3 weeks for 4–6 cycles.
  • Carboplatin (AUC = 5): A chemotherapy drug similar to cisplatin. Dosing may be based on AUC (area under the curve), a way to target overall drug exposure; in the ES-SCLC trial it is AUC = 5 every 3 weeks for 4–6 cycles.
  • Etoposide: A chemotherapy drug often paired with platinum chemotherapy. In the ES-SCLC trial it is given at 100 mg/m² on days 1, 2, and 3 every 3 weeks for 4–6 cycles.
  • Adverse event: Any unwanted medical problem that happens during a study treatment. Trials often track treatment-related adverse events to understand safety.
  • CTCAE v5.0: A standard system used in cancer trials to grade (rate) the severity of side effects (adverse events).

References

  1. https://clinicaltrials.gov/study/NCT06095583
  2. https://clinicaltrials.gov/study/NCT06732258