Subcutaneous amivantamab (ami) in patients (pts) with advanced solid malignancies: The PALOMA study—Updated safety and identification of the recommended phase 2 dose.
Bibliographic record
Abstract
9126 Background: Ami, an EGFR-MET bispecific antibody, is approved for pts with advanced EGFR exon 20 insertion non-small cell lung cancer after progression on platinum-based chemotherapy. Intravenous (IV) delivery is associated with infusion-related reactions (IRRs) in 67% of pts, requiring splitting the first dose over 2 days (Park Ann Oncol 2021;32[suppl_5]:S981). PALOMA (NCT04606381) is an ongoing phase 1b dose escalation study of subcutaneous (SC) ami ± rHuPH20 (a hyaluronidase that aids SC agent absorption) in pts with advanced solid tumors who may benefit from EGFR- or MET-directed therapy. Preliminary results showed SC ami was well tolerated, improved time and ease of administration, and meaningfully reduced IRRs (Krebs Cancer Res 2022;82:12_Supplement, CT198). We present updated safety results and identification of the recommended phase 2 dose (RP2D) for ami SC Q2W administration. Methods: PALOMA enrolled pts with various advanced solid tumors. Objectives were to evaluate administration feasibility, safety, and PK of low and high concentration formulations of ami SC (50 mg/mL ami ± rHuPH20 [Part 1; Cohorts 1a/b] and 160 mg/mL ami ± rHuPH20 [Part 2; Cohorts 2a/b, Cohort 3a, Cohort 5a]). Cohorts 1a/b and 2a/b received 1050 mg (1400 mg, ≥80 kg), Cohort 3a received 1600 mg (2240 mg, ≥80 kg), and Cohort 5a received 2560 mg (3360 mg, ≥80 kg). Cohorts 1-3 were dosed weekly for the first 4 weeks and Q2W thereafter. Cohort 5a was dosed weekly for the first 3 weeks and Q3W thereafter. Results: As of Jan 3, 2023, 81 pts were enrolled (16 pts in Part 1, 65 pts in Part 2) and majority had NSCLC (71; 88%). Median age was 64 years, 44 (54%) pts were female, and most pts were White (44; 54%) or Asian (34; 42%). Across all doses, IRRs were reported by 13 (16%) pts; all of grade 1-2. The most frequent manifestations of IRRs were chills (7%), pyrexia (7%), and asymptomatic tachycardia (4%). Treatment-emergent AEs (TEAEs) of rash were reported by 59 (73%) pts, with no grade ≥3. In total, 3 (4%) pts discontinued ami SC due to toxicity (2 pneumonitis, 1 asthenia). Grade ≥3 related TEAEs were reported by 3 (4%) pts (hypoalbuminemia, lymphopenia, hypertension). Full ami SC dosing on day 1 was feasible (≤7 min), obviating the need for split dosing. PK analysis confirmed that ami SC 1600 mg (2240 mg, ≥80 kg) Q2W resulted in similar exposure to the approved IV dose (1050 mg [1400 mg, ≥80 kg] Q2W). Compared to IV, ami SC resulted in lower Cmax and equal or higher Ctrough and AUC0-336h at Cycles 2 and 4. Based on these data, ami SC 1600 mg (2240 mg, ≥80 kg) was selected as the RP2D for ami SC Q2W administration. Conclusions: Ami SC was well tolerated with meaningful reductions in administration time and TEAEs. Ami SC provided a quantitative and qualitative improvement in the symptoms of IRRs vs historical IV rates. The identified RP2D for ami SC on the Q2W schedule achieved similar exposure as the approved IV dose. Clinical trial information: NCT04606381 .
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".