Initial results from the Phase 2 RedirecTT-1 study are in, and they’re impressive. The investigational combination therapy delivered a 78.9 percent overall response rate by simultaneously targeting GPRC5D and BCMA.
Data suggest a potential breakthrough with an off-the-shelf approach for patients battling extramedullary disease – a group with few treatment options and significant remaining unmet needs.
MILAN, June 15, 2025 /PRNewswire/ — Johnson & Johnson (NYSE: JNJ) revealed today promising new data from its Phase 2 RedirecTT-1 study, which is evaluating the combined use of TALVEY® (talquetamab-tgvs), the first U.S. FDA-approved GPRC5D-directed bispecific antibody, with TECVAYLI® (teclistamab-cqyv), the first FDA-approved BCMA-directed bispecific antibody. The results showcase a high overall response rate (ORR) with sustained responses in relapsed/refractory multiple myeloma (RRMM) patients having extramedullary disease (EMD) after being exposed to multiple classes of drugs. EMD is defined as plasmacytomas found in soft tissue or organs that are not connected to bone structures – conforming to International Myeloma Working Group (IMWG) criteria.1 The RedirecTT-1 study is the largest ever dedicated to this specific patient population. These findings were presented in a late-breaking oral presentation (Abstract #LB4001) at the 2025 European Hematology Association (EHA) Congress.
Extramedullary disease is an aggressive form of multiple myeloma wherein cancerous myeloma cells spread and form tumors (plasmacytomas) elsewhere, such as in soft tissues and organs. Patients with EMD often face limited treatment options and a poorer prognosis, due to its inherent complexity. This includes things like tumor heterogeneity, which often leads to low overall response rates and rapid relapses with current standard therapies. On average, TCE RRMM patients with EMD have an ORR of less than 40 percent and a median progression-free survival (PFS) of under 6 months.2
“The investigational combination of TALVEY and TECVAYLI has demonstrated deep, durable responses in those with relapsed or refractory multiple myeloma. And now, the data suggests similar potential in patients with extramedullary myeloma, an area where existing therapies often come up short,” stated Yael Cohen, M.D., Head of Myeloma Unit, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. “The dual targeting approach that hits both GPRC5D and BCMA may lead to a higher ORR and a more robust response by tackling the antigen-related escape that happens with existing therapies. These RedirecTT-1 trial results highlight the power of this novel, dual-targeting combination as a possible treatment option for this specific patient population.”
The Phase 2 RedirecTT-1 study enrolled 90 patients with TCE RRMM and confirmed EMD. Among these patients, 84.4 percent were triple-class refractory, 35.6 percent were penta-drug refractory, 20 percent had prior BCMA CAR-T therapy, and 8.9 percent had previously received a bispecific antibody.3 The combination of TALVEY® plus TECVAYLI® led to an impressive ORR of 78.9 percent (95 percent confidence interval [CI]; 69.0–86.8), with more than half of patients (54.4 percent) achieving a complete response or better.3 High response rates were also seen in patients previously exposed to BCMA CAR-T or anti-FcRH5 bispecific antibodies (83.3 percent ORR; 58.6-96.4 and 75 percent ORR; 34.9-96.8, respectively).3 With a median follow-up of 13.4 months, 66.2 percent of respondents remained in response at the data cutoff, indicating deep and durable responses.3 The combination therapy resulted in 61 percent of patients being progression-free and alive at one year.3 Furthermore, the combination demonstrated durable responses, with 64.1 percent of patients maintaining their response (median duration of response: 13.8 months) and 74.5 percent of patients alive at one year, while median overall survival was not yet reached.3
“Patients battling extramedullary myeloma, particularly those who have relapsed after other therapies, require more effective treatment options,” noted Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. “Our first-in-class bispecific antibodies, TALVEY and TECVAYLI, have revolutionized treatment for relapsed or refractory multiple myeloma. The RedirecTT-1 study confirms our dedication to developing innovative therapies, by attacking the disease from multiple angles by utilizing combinable and complementary regimens.”
The safety profile of the combination was consistent with the established profiles of each drug (TALVEY® and TECVAYLI® as monotherapies), and no new safety concerns were identified.3 Patients were given the option of switching to a once-a-month dosing schedule, which could improve tolerability. Discontinuation rates were low with the TALVEY® and TECVAYLI® combination due to adverse events (AEs).3 Four participants discontinued TALVEY® only.3 Reports of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were generally low grade.3 Out of the ten patients (11.1 percent) experiencing Grade 5 AEs, five were tied to infections and five were determined to be unrelated.3 The rate of severe infection was comparable to that seen with BCMA bispecific antibody monotherapies.3
About TALVEY®
TALVEY® (talquetamab-tgvs) received FDA approval in August 2023 as a first-in-class GPRC5D-targeting bispecific antibody. It is indicated for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.4 Since the FDA approval, more than 4,900 patients worldwide have been treated with TALVEY®. In Europe, the European Commission (EC) granted conditional marketing authorization (CMA) for TALVEY® ▼ (talquetamab) in August 2023 as a monotherapy. This is for the treatment of adults with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have shown disease progression on their latest therapy.5
TALVEY® is a bispecific T-cell engaging antibody that binds to the CD3 receptor on T-cells and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel multiple myeloma target. GPRC5D is highly expressed on the surface of multiple myeloma cells and nonmalignant plasma cells. Some healthy tissues, such as the epithelial cells of the skin and tongue, also express it.
About TECVAYLI®
TECVAYLI® (teclistamab-cqyv) received FDA approval in October 2022. It’s an off-the-shelf (or ready-to-use) antibody which is administered as a subcutaneous treatment for adults with relapsed or refractory multiple myeloma (RRMM), who have received at least four prior lines of therapy. Their prior therapies had to include a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.[6] As of the date of this release, more than 15,900 patients have been treated globally with TECVAYLI®. The European Commission (EC) granted TECVAYLI® conditional marketing authorization (CMA) in August 2022 as a monotherapy. This is for adults with RRMM who have already completed at least three prior therapies (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody) and have shown disease progression since their last therapy. In August 2023, the EC granted the approval of a Type II variation application for TECVAYLI®, providing the option for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients who have achieved a complete response (CR) or better for a minimum of six months. TECVAYLI® is a first-in-class, bispecific T-cell engager antibody therapy. It uses innovative science to activate the immune system by binding to the CD3 receptor which is expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) which is expressed on the surface of multiple myeloma cells, and some healthy B-lineage cells. In February 2024, the U.S. FDA approved the supplemental Biologics License Application (sBLA) for TECVAYLI® for a reduced dosing frequency of 1.5 mg/kg every two weeks in patients with relapsed or refractory multiple myeloma who have achieved and maintained a CR or better for a minimum of six months.
For more information, visit www.TECVAYLI.com.
About multiple myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, found in the bone marrow.7 In multiple myeloma, these plasma cells multiply and spread rapidly, thus taking the place of normal cells in the bone marrow with tumors.8 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.9 In 2024, more than 35,000 people were estimated to be diagnosed with multiple myeloma in the U.S., with more than 12,000 projected to die from the disease.10 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.[11] While some people diagnosed with multiple myeloma initially show no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, and kidney problems or infections.12,13
TALVEY® IMPORTANT SAFETY INFORMATION
INDICATION AND USAGE
TALVEY® (talquetamab-tgvs) is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TALVEY®. Initiate TALVEY® treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY® until CRS resolves or permanently discontinue based on severity.
Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life-threatening or fatal reactions, can occur with TALVEY®. Monitor patients for signs and symptoms of neurologic toxicity including ICANS during treatment and treat promptly. Withhold or permanently discontinue TALVEY® based on severity.
Because of the risk of CRS and neurologic toxicity, including ICANS, TALVEY® is available only through a restricted program called the TECVAYLI® and TALVEY® Risk Evaluation and Mitigation Strategy (REMS).
CONTRAINDICATIONS: None.
WARNINGS AND PRECAUTIONS
Cytokine Release Syndrome (CRS): TALVEY® can cause cytokine release syndrome, which includes life-threatening or fatal reactions. In the clinical trial, CRS occurred in 76% of patients who received TALVEY® at the recommended dosages, with Grade 1 CRS occurring in 57% of patients, Grade 2 in 17%, and Grade 3 in 1.5%. Recurrent CRS occurred in 30% of patients. Most events occurred following step-up dose 1 (29%) or step-up dose 2 (44%) at the recommended dosages. CRS occurred in 33% of patients with step-up dose 3 in the biweekly dosing schedule (N=153). CRS occurred in 30% of patients with the first 0.4 mg/kg treatment dose and in 12% of patients treated with the first 0.8 mg/kg treatment dose. The CRS rate for both dosing schedules combined was less than 3% for each of the remaining doses in Cycle 1 and less than 3% cumulatively from Cycle 2 onward. The median time to onset of CRS was 27 (range: 0.1 to 167) hours from the last dose, and the median duration was 17 (range: 0 to 622) hours. Clinical signs and symptoms of CRS include but are not limited to pyrexia, hypotension, chills, hypoxia, headache, and tachycardia. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).
Initiate therapy with step-up dosing and administer pre-treatment medications (corticosteroids, antihistamine, and antipyretics) prior to each dose of TALVEY® in the step-up dosing schedule to reduce the risk of CRS. Monitor patients following administration accordingly. In patients who experience CRS, pre-treatment medications should be administered prior to the next TALVEY® dose.
Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity, and consider further management per current practice guidelines. Withhold TALVEY® until CRS resolves or permanently discontinue based on severity.
Neurologic Toxicity including ICANS: TALVEY® can cause serious, or life-threatening neurologic toxicity or fatal neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS), including fatal reactions. In the clinical trial, neurologic toxicity, including ICANS, occurred in 55% of patients who received the recommended dosages, with Grade 3 or 4 neurologic toxicity occurring in 6% of patients. The most frequent neurologic toxicities were headache (20%), encephalopathy (15%), sensory neuropathy (14%), and motor dysfunction (10%).
ICANS was reported in 9% of 265 patients where ICANS was collected and who received the recommended dosages. Recurrent ICANS occurred in 3% of patients. Most patients experienced ICANS following step-up dose 1 (3%), step-up dose 2 (3%), step-up dose 3 of the biweekly dosing schedule (1.8%), or the initial treatment dose of the weekly dosing schedule (2.6%) (N=156) or the biweekly dosing schedule (3.7%) (N=109). The median time to onset of ICANS was 2.5 (range: 1 to 16) days after the most recent dose with a median duration of 2 (range: 1 to 22) days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.
Monitor patients for signs and symptoms of neurologic toxicity during treatment and treat promptly. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient and provide supportive care based on severity. Withhold or permanently discontinue TALVEY® based on severity and consider further management per current practice guidelines [see Dosage and Administration (2.5)].
Due to the potential for neurologic toxicity, patients receiving TALVEY® are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during the step-up dosing schedule and for 48 hours after completion of the step-up dosing schedule, and in the event of new onset of any neurological symptoms, until symptoms resolve.
TECVAYLI® and TALVEY® REMS: TALVEY® is available only through a restricted program under a REMS, called the TECVAYLI® and TALVEY® REMS because of the risks of CRS and neurologic toxicity, including ICANS.
Further information about the TECVAYLI® and TALVEY® REMS program is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064.
Oral Toxicity and Weight Loss: TALVEY® can cause oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis. In the clinical trial, 80% of patients had oral toxicity, with Grade 3 occurring in 2.1% of patients who received the recommended dosages. The most frequent oral toxicities were dysgeusia (49%), dry mouth (34%), dysphagia (23%), and ageusia (18%). The median time to onset of oral toxicity was 15 (range: 1 to 634) days, and the median time to resolution to baseline was 43 (1 to 530) days. Oral toxicity did not resolve to baseline in 65% of patients.
TALVEY® can cause weight loss. In the clinical trial, 62% of patients experienced weight loss, regardless of having an oral toxicity, including 29% of patients with Grade 2 (10% or greater) weight loss and 2.7% of patients with Grade 3 (20% or greater) weight loss. The median time to onset of Grade 2 or higher weight loss was 67 (range: 6 to 407) days, and the median time to resolution was 50 (range: 1 to 403) days. Weight loss did not resolve in 57% of patients who reported weight loss.
Monitor patients for signs and symptoms of oral toxicity. Counsel patients to seek medical attention should signs or symptoms of oral toxicity occur and provide supportive care as per current clinical practice, including consultation with a nutritionist. Monitor weight regularly during therapy. Evaluate clinically significant weight loss further. Withhold TALVEY® or permanently discontinue based on severity.
Infections: TALVEY® can cause infections, including life-threatening or fatal infections. Serious infections occurred in 16% of patients, with fatal infections in 1.5% of patients. Grade 3 or 4 infections occurred in 17% of patients. The most common serious infections reported were bacterial infection (8%), which included sepsis and COVID-19 (2.7%).
Monitor patients for signs and symptoms of infection prior to and during treatment with TALVEY® and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Withhold or consider permanent discontinuation of TALVEY® as recommended, based on severity.
Cytopenias: TALVEY® can cause cytopenias, including neutropenia and thrombocytopenia. In the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 35% of patients, and Grade 3 or 4 decreased platelets occurred in 22% of patients who received TALVEY®. The median time to onset for Grade 3 or 4 neutropenia was 22 (range: 1 to 312) days, and the median time to resolution to Grade 2 or lower was 8 (range: 1 to 79) days. The median time to onset for Grade 3 or 4 thrombocytopenia was 12 (range: 2 to 183) days, and the median time to resolution to Grade 2 or lower was 10 (range: 1 to 64) days. Monitor complete blood counts during treatment and withhold TALVEY® as recommended, based on severity.
Skin Toxicity: TALVEY® can cause serious skin reactions, including rash, maculo-papular rash, erythema, and erythematous rash. In the clinical trial, skin reactions occurred in 62% of patients, with Grade 3 skin reactions in 0.3%. The median time to onset was 25 (range: 1 to 630) days. The median time to improvement to Grade 1 or less was 33 days.
Monitor for skin toxicity, including rash progression. Consider early intervention and treatment to manage skin toxicity. Withhold TALVEY® as recommended based on severity.
Hepatotoxicity: TALVEY® can cause hepatotoxicity. Elevated ALT occurred in 33% of patients, with Grade 3 or 4 ALT elevation occurring in 2.7%; elevated AST occurred in 31% of patients, with Grade 3 or 4 AST elevation occurring in 3.3%. Grade 3 or 4 elevations of total bilirubin occurred in 0.3% of patients. Liver enzyme elevation can occur with or without concurrent CRS.
Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TALVEY® or consider permanent discontinuation of TALVEY®, based on severity [see Dosage and Administration (2.5)].
Embryo-Fetal Toxicity: Based on its mechanism of action, TALVEY® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TALVEY® and for 3 months after the last dose.
Adverse Reactions: The most common adverse reactions (≥20%) are pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache.
The most common Grade 3 or 4 laboratory abnormalities (≥30%) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased.
Please read full Prescribing Information, including Boxed WARNING, for TALVEY®.
TECVAYLI® IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI®. Initiate treatment with TECVAYLI® step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI® until CRS resolves or permanently discontinue based on severity.
Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI®. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI® until neurologic toxicity resolves or permanently discontinue based on severity.
TECVAYLI® is available only through a restricted program called the TECVAYLI® and TALVEY® Risk Evaluation and Mitigation Strategy (REMS).
INDICATION AND USAGE
TECVAYLI® (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
WARNINGS AND PRECAUTIONS
Cytokine Release Syndrome – TECVAYLI® can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI® at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI®. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).
Initiate therapy according to TECVAYLI® step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI® accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI® based on severity.
TECVAYLI® is available only through a restricted program under a REMS.
Neurologic Toxicity including ICANS – TECVAYLI® can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).
In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI® at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI®.
In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI® at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI®. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.
Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI® based on severity per recommendations and consider further management per current practice guidelines.
Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI® step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.
TECVAYLI® is available only through a restricted program under a REMS.
TECVAYLI® and TALVEY® REMS – TECVAYLI® is available only through a restricted program under a REMS called the TECVAYLI® and TALVEY® REMS because of the risks of CRS and neurologic toxicity, including ICANS.
Hepat
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