Randomized Phase 2 Study of Subcutaneous Daratumumab Plus Carfilzomib/Dexamethasone Versus Carfilzomib/Dexamethasone Alone in Patients with Multiple Myeloma Who Have Been Previously Treated with Intravenous Daratumumab to Evaluate Retreatment (LYNX)
Bibliographic record
Abstract
Background: Daratumumab is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. The intravenous (IV) formulation of daratumumab is approved in many countries for use as monotherapy in relapsed/refractory multiple myeloma (RRMM), and in combination with standard-of-care regimens in RRMM and patients with NDMM who are transplant ineligible. A subcutaneous (SC) formulation of daratumumab is currently under investigation in several ongoing studies. In the phase 3 COLUMBA study, daratumumab SC was shown to be non-inferior to daratumumab IV, demonstrating similar efficacy and pharmacokinetics, with a significantly decreased rate of infusion-related reactions and reduced administration time. The randomized phase 2 LYNX (MMY2065) study will evaluate the efficacy and safety of retreatment with subcutaneous daratumumab in patients with RRMM who were previously exposed to daratumumab IV therapy. Study Design and Methods: In this ongoing, multicenter, open-label, randomized phase 2 study, approximately 230 patients with prior exposure to daratumumab will be randomized 1:1 to receive daratumumab plus carfilzomib and dexamethasone (D-Kd) or carfilzomib and dexamethasone (Kd) alone. Patients must have received 1 to 2 prior lines of therapy (at least one of which included daratumumab IV) with the daratumumab-based therapy completed ≥3 months prior to randomization. Eligible patients must have achieved a partial response or better (as defined by International Myeloma Working Group [IMWG] criteria) to daratumumab-based therapy, with a duration of response of ≥4 months. Patients must not have discontinued daratumumab due to a daratumumab-related adverse event or received prior treatment with carfilzomib. All patients will receive 20 mg/m2 carfilzomib IV on Day 1 of Cycle 1, escalated to 70 mg/m2 on Days 8 and 15; carfilzomib 70 mg/m2 will be administered on Days 1, 8, and 15 of each 28-day cycle thereafter. Dexamethasone 40 mg will be administered (IV or PO) QW for Cycles 1-9 and then on Days 1, 8, and 15 from Cycle 10 onwards. Patients in the D-Kd group will also receive daratumumab SC (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; ENHANZE® drug delivery technology, Halozyme, Inc.]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter. The primary endpoint is the rate of patients achieving a very good partial response or better. Secondary endpoints include overall response rate, rate of patients achieving complete response or better, progression-free survival, overall survival, overall MRD-negativity rate, time to next treatment, pharmacokinetics, and safety. The ClinicalTrials.gov identifier is NCT03871829. Disclosures Bahlis: Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Zonder:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Intellia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Caelum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wroblewski:Janssen: Employment, Equity Ownership. Qi:Janssen: Employment. Renaud:Janssen: Employment, Equity Ownership. Jackson:Janssen: Employment, Equity Ownership. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: This presentation/paper includes information/discussion of a subcutaneous formulation of daratumumab, which is currently under investigation in several clinical trials, but has not yet been approved. The intravenous formulation of daratumumab is approved as monotherapy and in combination with standard-of-care regimens for the treatment of MM.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.005 |
| Insufficient payload (model declined to judge) | 0.011 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".