NCIC IND.190: A phase I trial of MK-0646 in combination with cisplatin and etoposide in extensive-stage small cell lung cancer (ES SCLC).
Bibliographic record
Abstract
7093 Background: Increased serum levels of insulin like growth factor (IGF), plus overexpression of the IGF-receptor (IGFR) are implicated in SCLC cell growth and proliferation, making suppression of the IGFR a potential therapeutic target. MK-0646 is a monoclonal antibody directed against the IGFR. The aim of this study was to determine the recommended phase II dose (RP2D) of cisplatin, etoposide plus MK-0646. Methods: We conducted a phase I study of two dose levels of MK-0646 (DL1 5mg/kg, DL2 10mg/kg IV weekly) in combination with cisplatin (25mg/m 2 ) and etoposide (100mg/m 2 ) IV D1-3, q21d, for patients with chemotherapy-naive ES SCLC, PS 0-2. Patients with treated stable brain metastases were eligible. Patients completing 4-6 cycles of combination therapy could continue single agent MK-0646 until disease progression. Primary outcome was determination of the RP2D. Secondary outcomes included ORR (RECIST 1.1), and toxicity (CTCAEv3). Results: A total of 12 patients were treated (DL1 – 3, DL2 – 9). The median age was 63 years (48-70), with 6 males and 6 females. Most subjects were good ECOG PS (PS 1 – 8, PS 2 – 4) and had 4 or more sites of disease (n=8). No DLTs were observed in DL1 or DL2. In an expanded DL2 cohort, 1 patient died from neutropenic sepsis during cycle 1. The median number of treatment cycles of chemotherapy was 4 (DL1) or 5 (DL2) and MK-0646 was 6 (DL1&2). Dose delays were observed for chemotherapy (DL1 - 2, DL2 – 6) and MK-0646 (DL1 – 3, DL2 – 7). The confirmed ORR was 72.7% (PR 8, SD 2, PD 1, non-evaluable 1). Grade ≥3 toxicities (any cycle) occurring in more than 1 patient included: neutropenia (92%); thrombocytopenia (25%); leukopenia (50%); anemia (17%); fatigue (33%); joint pain (17%); thrombosis (25%). Grade 2 or 3 hyperglycemia was observed in 1 of 3 (DL1) and 5 of 9 (DL2). Eight SAEs were observed in 3 patients (thrombosis, febrile neutropenia, infection, syncope, fatigue 2, dyspnea, back pain). Conclusions: MK-0646 can be combined at full dose with standard doses of cisplatin and etoposide (25mg/m 2 and 100mg/m 2 D1-3) with a RP2D of MK-0646 10mg/kg/week. The observed toxicities are consistent with that expected from cisplatin and etoposide except for hyperglycemia, which appears dose dependent.
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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".