A Phase I/II Study of AZD0305, a Novel Antibody-Drug Conjugate (ADC) Targeting GPRC5D, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)
Bibliographic record
Abstract
Background and Significance: GPRC5D (G Protein-coupled Receptor, Class C, Group 5, Member D) is a known therapeutic target for multiple myeloma (MM). The GPRC5D bispecific T-cell-engager talquetamab was conditionally approved recently by the FDA and EMA for the treatment of RRMM in adults with at least 4 prior lines of therapy. However, there is still a need to explore additional approaches to target this protein without reliance on immune fitness. AZD0305 is a first-in-class ADC that binds specifically to GPRC5D. AZD0305 has shown preclinical activity against MM and has the potential to be active in patients with RRMM who have exhausted or cannot tolerate standard of care options. In addition to payload-mediated cytotoxicity, AZD0305 can potentially drive the killing of tumor cells through antibody-dependent cellular cytotoxicity. Study Design and Methods: NCT06106945 is a modular Phase I/II, open-label, multicenter, dose escalation, and dose expansion/optimization study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and preliminary efficacy of AZD0305 in patients with RRMM. Module 1 includes Phase Ia (Dose escalation) and Phase Ib (Dose expansion/optimization). The total enrollment is estimated to be approximately 84. Patients with RRMM >18 years of age, treated with at least 3 prior lines of treatment including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody are eligible. Patients must have measurable disease by IMWG criteria and an ECOG performance status of ≤2. Patients with peripheral neuropathy Grade ≥2, known COPD, or previous history of interstitial lung disease, uncontrolled cardiovascular disease and primary refractory MM are excluded. Further, patients who previously received anti-GPRC5D or MMAE-containing treatment are excluded. The primary endpoints of the phase I include occurrence of dose-limiting toxicities (dose escalation only) and incidence and severity of adverse events and serious adverse events. Secondary endpoints include but are not limited to objective response rate, duration of response, progression free survival, pharmacokinetics of AZD0305 and immunogenicity of AZD0305. This study is currently recruiting patients for phase I in North America, Europe, Asia and Australia.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".