A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma: A phase I clinical trial

Figures & data

Table I. Baseline patient demographics and clinical characteristics of the entire cohort.

Characteristics	All patients phase Ia	All patients phase Ib	Subgroup patients NSCLC
Total included	16	39	19
Age (years; median, range)	58.5 (25–83)	64.0 (27–80)	65.0 (54–83)
Sex
Male	9	24	10
Female	7	15	9
Performance status
0	8	13	3
1	5	21	14
2	3	5	2
Tumor type
NSCLC, adeno		7	7
NSCLC, squamous	5	10	12
Prostate		7
Gastrointestinal tumor	6	4
Malignant melanoma	1	4
Ovarian cancer		2
Other	4 (salivary gland carcinoma, sinonasal undifferentiated carcinoma, chondrosarcoma, SCLC)	5 (salivary gland carcinoma, chondrosarcoma, B-cell lymphoma, breast and kidney cancer)
Prior therapy
Surgery	8	21	4
Radiotherapy (excluding palliation)	9	20	12
Chemotherapy (including palliation)	15 (7, 3 + regimens)	39 (26, 3 + regimens)	19 (13, 3 + regimens)
Hormone/immunotherapy	3	11	0
Smoking status
Never smoker			2
Ex-smoker			13
Current smoker			4
Stage at diagnosis
Ia			2
Ib			1
IIa			0
IIb			3
IIIa			8
IIIb			3
IV			2
Stage at inclusion
IIIa			6
IIIb			1
IV			12

Table II. Possibly/probably related adverse events in phase Ib.

Adverse event reported Preferred term	No. of related AEs (no. of pat)	No. of CTCAE Grade 1–2 (no of pat)	No. of CTCAE Grade 3 (no of pat)	No. of CTCAE Grade 4 (no of pat)	No. of CTCAE Grade 5 (no of pat)
Leukopenia	15 (11)	1 (1)	4 (3)	10 (8)	0 (0)
Neutropenia	14 (10)	0 (0)	3 (2)	10 (8)	1 (1)
Alopecia	9 (9)	9 (9)	0 (0)	0 (0)	0 (0)
Fatigue	7 (6)	7 (6)	0 (0)	0 (0)	0 (0)
Oral candidiasis	7 (6)	6 (5)	1 (1)	0 (0)	0 (0)
Febrile neutropenia	6 (5)	0 (0)	0 (0)	6 (5)	0 (0)
Anemia	4 (4)	4 (4)	0 (0)	0 (0)	0 (0)
Thrombocytopenia	3 (3)	0 (0)	0 (0)	3 (3)	0 (0)
Nausea	2 (2)	2 (2)	0 (0)	0 (0)	0 (0)
Oral dysaesthesia	2 (1)	2 (1)	0 (0)	0 (0)	0 (0)
Sepsis	1 (1)	0 (0)	1 (1)	0 (0)	0 (0)
Rash pustular	1 (1)	1 (1)	0 (0)	0 (0)	0 (0)
Pyrexia	1 (1)	1 (1)	0 (0)	0 (0)	0 (0)
Abdominal pain	1 (1)	1 (1)	0 (0)	0 (0)	0 (0)
Dry eyes	1 (1)	1 (1)	0 (0)	0 (0)	0 (0)
Xerostomia	1 (1)	1 (1)	0 (0)	0 (0)	0 (0)
Dysgeusia	1 (1)	1 (1)	0 (0)	0 (0)	0 (0)
Eczema	1 (1)	1 (1)	0 (0)	0 (0)	0 (0)
Erythema	1 (1)	1 (1)	0 (0)	0 (0)	0 (0)

Figure 1. Kaplan-Meier plot for the overall survival of the total population (n = 49) with one patient alive at cut-off.

Figure 2. Kaplan-Meier plot for the overall survival (with one patient alive at cut-off) and the progression-free survival of the total population in multidose (Phase Ib) with a treatment duration longer than 2 weeks with single agent AXL1717 (n = 34).

Figure 3. Kaplan-Meier plot for the overall survival (with no patients alive at cut-off) and progression-free survival of the 15 patients with NSCLC with treatment duration longer than 2 weeks with single agent AXL1717.

Figure 4. A and B Transaxial images at baseline and 3-month follow-up with FDG PET-CT and contrast-enhanced CT (CECT) in a patient with a primary NSCLC (solid arrows) in the left lung and pleural metastases (cross marked). A) shows a significant reduction in the primary tumor metabolism measured in maximum standardized uptake value (SUVmax, g/mL) and size on CECT evaluated with the RECIST 1.1 criteria (LD, transaxial longest diameter) at 3-month follow-up. B) shows a concordant significant reduction in the pleural metastases with total metabolic regress on FDG PET-CT after treatment.