TALVEY® (talquetamab-tgvs) and DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) based combination shows deep and durable responses in patients with relapsed or refractory multiple myeloma

Rhea-AI Summary

Johnson & Johnson announced updated results from the Phase 1b TRIMM-2 study evaluating TALVEY® (talquetamab-tgvs) combined with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) and pomalidomide in relapsed or refractory multiple myeloma patients. The study showed an overall response rate (ORR) of 82 percent. In the weekly dosing arm, the ORR was 100 percent, with 56 percent achieving complete response or better. The biweekly arm achieved 76 percent ORR. The median duration of response in the biweekly arm was 26.4 months, with median progression-free survival of 20.3 months. The safety profile reflected known profiles of the individual therapies, with manageable side effects. These results support further investigation of TALVEY® in combination with DARZALEX FASPRO®, currently being studied in the Phase 3 MonumenTAL-3 study.

Positive

• 100% overall response rate in weekly dosing arm
• 56% of patients achieved complete response or better in weekly dosing arm
• 82% overall response rate across all dosing arms
• 26.4 months median duration of response in biweekly arm
• 20.3 months median progression-free survival in biweekly arm
• 82.8% overall response rate in patients with prior bispecific antibody exposure
• Safety profile consistent with known profiles of individual therapies

Negative

• High incidence of neutropenia (83.3% in weekly arm, 79.7% in biweekly arm)
• Grade 3/4 infection rates of 16.7% in weekly arm and 37.3% in biweekly arm

Insights

Medical Research Analyst

The latest data from the Phase 1b TRIMM-2 study demonstrates impressive efficacy for the combination of TALVEY® (talquetamab-tgvs) with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) and pomalidomide in relapsed/refractory multiple myeloma patients. Key findings include:

• 100% overall response rate with 56% complete response or better in the weekly dosing arm
• 82% overall response rate across all patients
• Median duration of response of 26.4 months and progression-free survival of 20.3 months in the biweekly arm
• Strong efficacy in difficult-to-treat subgroups, including anti-CD38 refractory and prior CAR-T therapy patients

The safety profile appears manageable, with mostly low-grade on-target adverse events. These results support further investigation of this combination, particularly in earlier lines of therapy. The ongoing Phase 3 MonumenTAL-3 study will be important in confirming these promising results in a larger patient population.

Financial Analyst

This clinical data is highly positive for Johnson & Johnson's (JNJ) oncology portfolio, particularly in the competitive multiple myeloma space. Key financial implications include:

• Potential for expanded market share in multiple myeloma treatment
• Increased revenue streams from both TALVEY® and DARZALEX FASPRO®
• Possibility of earlier line treatment, which could significantly increase the patient population and market size
• Strengthened competitive position against other multiple myeloma treatments

If approved, this combination could become a new standard of care, driving long-term growth for JNJ's hematology franchise. The $353 billion market cap company could see a meaningful impact on its oncology segment revenues, which is important as it faces patent cliffs in other areas. Investors should monitor the progress of the Phase 3 MonumenTAL-3 study as a key catalyst for JNJ's future performance in this therapeutic area.

Updated data show 100 percent overall response rate with 56 percent of patients achieving complete response or better with weekly dosing, supporting the combinability of the GPRC5D bispecific antibody

Safety profile, including infection rates, similar to TALVEY^® and DARZALEX FASPRO^® monotherapies

RIO DE JANEIRO, Sept. 27, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced updated results from the investigational Phase 1b TRIMM-2 study evaluating the combination of TALVEY^® (talquetamab-tgvs) with DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj) and pomalidomide in patients with relapsed or refractory multiple myeloma that demonstrated an overall response rate (ORR) of 82 percent, further supporting the investigation of this combination. These data were featured in an oral presentation at the 2024 International Myeloma Society Annual Meeting (Abstract #OA – 01).

The results from the Phase 1b TRIMM-2 study evaluating TALVEY^®, the first bispecific T-cell engager to target GPRC5D, combined with DARZALEX FASPRO^®, the first subcutaneous anti-CD38 monoclonal antibody, and pomalidomide included patients who received at least three prior lines of therapy, including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), or were double refractory to a PI and IMiD and had not received anti-CD38 therapy in the previous 90 days.¹ 

At data cutoff, 77 patients had received TALVEY^® in doses of 0.4 mg/kg weekly (QW) or 0.8 mg/kg biweekly (Q2W), with step-up doses, combined with DARZALEX FASPRO^® and pomalidomide. In the QW arm (n=18), the overall response rate (ORR) was 100 percent, with 56 percent having a complete response (CR) or better. The Q2W arm (n=59) achieved 76 percent ORR, with 56 percent achieving CR or better. The median duration of response (DOR) in the Q2W arm was 26.4 months, and the median progression-free survival (PFS) was 20.3 months. Results showed 52 percent of patients who are anti-CD38 refractory (n=64) achieved CR or better and 70.8 percent of patients who received prior chimeric antigen receptor T cell (CAR-T) therapy (n=24) achieved CR or better. Patients who had received prior bispecific antibodies (n=29) achieved an 82.8 percent ORR.¹ 

"The deep and durable responses shown in these latest results from TRIMM-2 further support the potential of TALVEY in combination with DARZALEX FASPRO, which has become a standard of care in multiple myeloma, and pomalidomide," said Nizar Bahlis, M.D., Associate Professor, Arnie Charbonneau Cancer Institute, University of Calgary and presenting author.* "With high overall response rates seen across cohorts, this combination shows potential for significant disease control and survival in patients who have received multiple lines of prior therapy, including exposure to prior bispecific antibodies."

The safety profile of this combination reflected the known profiles of TALVEY^®, DARZALEX FASPRO^® and pomalidomide. Despite the incidence of neutropenia (83.3 percent in the QW arm and 79.7 percent in the Q2W arm) being high, the Grade 3/4 infection rate was generally low (16.7 percent and 37.3 percent, respectively). The majority of on-target, off-tumor treatment-related adverse events (TRAEs), including oral (100 percent in the QW arm, 84.7 percent in Q2W arm), skin (88.9 percent, 67.8 percent), nail (83.3 percent, 55.9 percent) and weight decrease (66.7 percent, 49.2 percent) were low-grade (Grade 1/2) and did not lead to discontinuation of therapy. These results support further investigation of TALVEY^® in combination with DARZALEX FASPRO^®, with or without pomalidomide, in patients who have received earlier lines of therapy, including a proteasome inhibitor and lenalidomide, which is currently being investigated in the registrational, Phase 3 MonumenTAL-3 study.¹

"We continue to be encouraged by the potential versatility of TALVEY as a combination partner with other therapies to address unmet needs for patients with relapsed or refractory multiple myeloma who have limited treatment options at this advanced stage," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Innovative Medicine at Johnson & Johnson. "By simultaneously targeting GPRC5D and CD38 on myeloma cells with the combination of TALVEY and DARZALEX FASPRO, we are aiming to attack multiple myeloma in different ways to help improve outcomes for patients with this serious illness and limited treatment options."

Additional data underscoring the combinability of TALVEY^® from the RedirecTT-1 study will also be presented at IMS. Results from the TRIMM-2 study were previously presented at the 2023 ASCO Annual Meeting.

About TRIMM-2 Study
The TRIMM-2 (NCT04108195) study is an ongoing Phase 2 study of DARZALEX FASPRO^® regimens in combination with TALVEY^® for the treatment of patients with multiple myeloma. The primary objectives of the TRIMM-2 study were to identify the Phase 2 dose (RP2D) for each component of the treatment combination (Part One); characterize the safety of the treatment combination at the RP2D (Part 2); and assess antitumor activity, pharmacokinetics and pharmacodynamics for the combination treatment (Part 3). Patients in the study (N=65) all had multiple myeloma and had received a minimum three prior lines of therapy or were double refractory to a proteasome inhibitor (PI) and an immunomodulatory agent; patients who had been exposed or refractory to an anti-CD38 therapy more than ninety days prior to the start of the trial were also included, as well as those refractory to anti-CD38 therapy.

About MonumenTAL-3
The MonumenTAL-3 (NCT05455320) study is an ongoing Phase 3 study of TALVEY^® in combination with DARZALEX FASPRO^® with or without pomalidomide compared to DARZALEX FASPRO^® combined with pomalidomide and dexamethasone in patients with relapsed of refractory multiple myeloma who have received at least one prior line of therapy.   

About Multiple Myeloma
Multiple myeloma is a blood cancer affecting a type of white blood cell called plasma cells found in the bone marrow.² In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.³ Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.⁴ In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.⁵ People with multiple myeloma have a 5-year survival rate of 59.8 percent.⁶ While some people diagnosed with multiple myeloma initially have 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, kidney problems or infections.^{7, 8}

About TALVEY^® 
TALVEY^® (talquetamab-tgvs) received approval from the U.S. FDA in August 2023 as a first-in-class GPRC5D-targeting bispecific antibody 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 antibody.⁹ Since FDA approval, 1,500 patients were treated with TALVEY^®. The European Commission (EC) granted conditional marketing authorization (CMA) of TALVEY^® in August 2023 as monotherapy for the treatment of adult patients 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 demonstrated disease progression on the last therapy.¹⁰

TALVEY^® is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel multiple myeloma target which is highly expressed on the surface of multiple myeloma cells and non-malignant plasma cells, as well as some healthy tissues such as epithelial cells of the skin and tongue. 

For more information, visit www.TALVEY.com. 

About DARZALEX FASPRO^®
DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.¹¹ It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO^® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE^® drug delivery technology.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

For more information, visit https://www.darzalexhcp.com.

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. Withhold or 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, including 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. 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, including immune effector cell-associated neurotoxicity syndrome (ICANS), including fatal reactions. In the clinical trial, neurologic toxicity 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. 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 of 5% or greater, regardless of having an oral toxicity, including 28% 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 permanently discontinuing 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^®. 

DARZALEX FASPRO^® INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS
DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

• In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
• In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
• In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
• In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
• In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)
• In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
• As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS 
DARZALEX FASPRO^® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation. 

WARNINGS AND PRECAUTIONS 

Hypersensitivity and Other Administration Reactions 
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO^®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO^®. 

Systemic Reactions 
In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO^® as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 0.7%, Grade 4: 0.1%). Systemic administration-related reactions occurred in 7% of patients with the first injection, 0.2% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87%) occurred on the day of DARZALEX FASPRO^® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.

Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO^®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO^® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO^® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO^®.

Local Reactions 
In this pooled safety population, injection-site reactions occurred in 7% of patients, including Grade 2 reactions in 0.8%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO^®. Monitor for local reactions and consider symptomatic management.

Neutropenia
Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO^® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO^®, higher rates of Grade 3-4 neutropenia were observed.

Thrombocytopenia 
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX FASPRO^® until recovery of platelets. 

Embryo-Fetal Toxicity 
Based on the mechanism of action, DARZALEX FASPRO^® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO^® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO^® and for 3 months after the last dose. 

The combination of DARZALEX FASPRO^® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy. 

Interference With Serological Testing 
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted. 

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO^®. Type and screen patients prior to starting DARZALEX FASPRO^®. 

Interference With Determination of Complete Response 
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO^®-treated patients with IgG kappa myeloma protein. 

ADVERSE REACTIONS 

In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO^® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral neuropathy, peripheral sensory neuropathy, constipation, pneumonia, edema, peripheral edema, musculoskeletal pain, and rash.

The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO^® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin. 

Please click here to read full Prescribing Information for DARZALEX FASPRO^®.

About Johnson & Johnson 
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, Janssen Biotech, Inc. and Janssen Global Services, LLC are Johnson & Johnson companies.

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of TALVEY^® or DARZALEX FASPRO^®.  The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. 

* Nizar Bahlis, M.D., Associate Professor, Arnie Charbonneau Cancer Institute, University of Calgary, has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. 

¹ Bahlis, N., et al. Talquetamab + daratumumab + pomalidomide in patients with relapsed/refractory multiple myeloma: Results from the phase 1b TRIMM-2 study. IMS 2024. September 27, 2024.
² Rajkumar SV. Multiple Myeloma: 2020 Update on Diagnosis, Risk-Stratification and Management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178
³ National Cancer Institute. Plasma Cell Neoplasms. Accessed January 17, 2024. Available at: https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq
⁴ Multiple Myeloma. City of Hope, 2022. Multiple Myeloma: Causes, Symptoms & Treatments. Accessed May 2024. https://www.cancercenter.com/cancer-types/multiple-myeloma
⁵ American Cancer Society. Myeloma Cancer Statistics. Accessed May 2024. Available at: https://cancerstatisticscenter.cancer.org/types/myeloma
⁶ SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. Accessed: September 2024. https://seer.cancer.gov/explorer/
⁷ American Cancer Society. What is Multiple Myeloma? Accessed May 2024. Available at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html
⁸ American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. Accessed May 2024. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html
⁹ TALVEY^® U.S. Prescribing Information, August 2023.
¹⁰ European Medicines Agency. TALVEY Summary of Product Characteristics. August 2023.
¹¹ DARZALEX FASPRO^® U.S. Prescribing Information. July 2024.

Media contacts:  Satu Glawe  sschmid2@its.jnj.com      Christie Corbett Ccorbet6@its.jnj.com

Investor contact:  Raychel Kruper  investor-relations@its.jnj.com    U.S. medical inquiries:  +1 800 526-7736

 

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SOURCE Johnson & Johnson

FAQ

What was the overall response rate for TALVEY and DARZALEX FASPRO combination in the TRIMM-2 study for JNJ?

The overall response rate (ORR) across all dosing arms was 82 percent. In the weekly dosing arm, the ORR was 100 percent, while in the biweekly arm, it was 76 percent.

What was the complete response rate for TALVEY and DARZALEX FASPRO in relapsed or refractory multiple myeloma patients for JNJ?

In both the weekly and biweekly dosing arms, 56 percent of patients achieved a complete response (CR) or better.

What was the median duration of response for TALVEY and DARZALEX FASPRO in the TRIMM-2 study by JNJ?

The median duration of response (DOR) in the biweekly arm was 26.4 months.

What was the progression-free survival for TALVEY and DARZALEX FASPRO combination in the TRIMM-2 study by JNJ?

The median progression-free survival (PFS) in the biweekly arm was 20.3 months.

What were the main side effects of TALVEY and DARZALEX FASPRO combination in the TRIMM-2 study by JNJ?

The main side effects included neutropenia, oral, skin, and nail-related adverse events, and weight decrease. Most were low-grade (Grade 1/2) and did not lead to treatment discontinuation.