Table 1. Baseline Characteristics of Patients in the Dose-Finding Phase and Dose-Expansion Cohorts.
| Characteristic | Patients, No. (%) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose-finding phase (n = 12) | NSCLC (n = 42) | DDR+ NSCLC (n = 5) | TNBC (n = 22) | HR+, ERBB2−, DDR+ BC (n = 23) | OC (n = 20) | BRCA-alt OC (n = 11) | UC (n = 40) | mCRPC (n = 21) | DDR+ mCRPC (n = 18) | BRCA/ATM alt (n = 9)a | |
| Age, y | |||||||||||
| <65 | 6 (50.0) | 15 (35.7) | 4 (80.0) | 15 (68.2) | 17 (73.9) | 12 (60.0) | 7 (63.6) | 16 (40.0) | 8 (38.1) | 3 (16.7) | 5 (55.6) |
| ≥65 | 6 (50.0) | 27 (64.3) | 1 (20.0) | 7 (31.8) | 6 (26.1) | 8 (40.0) | 4 (36.4) | 24 (60.0) | 13 (61.9) | 15 (83.3) | 4 (44.4) |
| Median (IQR) | 63.5 (55-70) | 67.5 (61-73) | 63.0 (59-64) | 56.5 (48-67) | 51.0 (42-66) | 62.5 (56-68) | 59.0 (56-70) | 66.5 (57-72) | 65.0 (57-67) | 70.5 (68-79) | 62.0 (59-69) |
| Sex | |||||||||||
| Women | 3 (25.0) | 9 (21.4) | 2 (40.0) | 22 (100) | 22 (95.7) | 20 (100) | 11 (100) | 14 (35.0) | 0 | 0 | 3 (33.3) |
| Men | 9 (75.0) | 33 (78.6) | 3 (60.0) | 0 | 1 (4.3) | 0 | 0 | 26 (65.0) | 21 (100) | 18 (100) | 6 (66.7) |
| ECOG PS | |||||||||||
| 0 | 4 (33.3) | 5 (11.9) | 1 (20.0) | 12 (54.5) | 12 (52.2) | 9 (45.0) | 8 (72.7) | 16 (40.0) | 4 (19.0) | 6 (33.3) | 1 (11.1) |
| 1 | 8 (66.7) | 37 (88.1) | 4 (80.0) | 10 (45.5) | 11 (47.8) | 11 (55.0) | 3 (27.3) | 24 (60.0) | 17 (81.0) | 12 (66.7) | 8 (88.9) |
| PD-L1 statusb | |||||||||||
| High | NA | 3 (7.1) | 1 (20.0) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Low | NA | 8 (19.0) | 1 (20.0) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Positive | NA | 0 | 0 | 8 (36.4) | 3 (13.0) | 5 (25.0) | 5 (45.5) | 13 (32.5) | 1 (4.8) | 2 (11.1) | 0 |
| Negative | NA | 22 (52.4) | 2 (40.0) | 6 (27.3) | 16 (69.6) | 13 (65.0) | 4 (36.4) | 19 (47.5) | 12 (57.1) | 12 (66.7) | 3 (33.3) |
| Unknownc | NA | 9 (21.4) | 1 (20.0) | 8 (36.4) | 4 (17.4) | 2 (10.0) | 2 (18.2) | 8 (20.0) | 8 (38.1) | 4 (22.2) | 6 (66.7) |
| DDR statusd | |||||||||||
| Positive | NA | 12 (28.6) | 3 (60.0) | 11 (50.0) | 19 (82.6) | 5 (25.0) | 10 (90.9) | 18 (45.0) | 7 (35.0) | 16 (88.9) | 8 (88.9) |
| Negative | NA | 30 (71.4) | 2 (40.0) | 11 (50.0) | 4 (17.4)e | 15 (75.0) | 1 (9.1) | 22 (55.0) | 13 (65.0) | 2 (11.1) | 1 (11.1) |
| TNM stage | |||||||||||
| III | 0 | 0 | 0 | 1 (4.5) | 1 (4.3) | 4 (20.0) | 3 (27.3) | 2 (5.0) | 0 | 0 | 1 (11.1) |
| IIIA | 0 | 3 (7.1) | 0 | 1 (4.5) | 0 | 0 | 0 | 3 (7.5) | 0 | 0 | 0 |
| IIIB | 0 | 6 (14.3) | 1 (20.0) | 0 | 0 | 2 (10.0) | 1 (9.1) | 2 (5.0) | 1 (4.8) | 0 | 0 |
| IV | 10 (83.3) | 33 (78.6) | 4 (80.0) | 20 (90.9) | 22 (95.7) | 13 (65.0) | 7 (63.6) | 33 (82.5) | 20 (95.2) | 18 (100) | 7 (77.8) |
| IVA | 1 (8.3) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| IVB | 1 (8.3) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not reported | 0 | 0 | 0 | 0 | 0 | 1 (5.0) | 0 | 0 | 0 | 0 | 1 (11.1) |
| Prior anticancer therapies for advanced diseasef | |||||||||||
| 0 | 0 | 20 (47.6) | 2 (40.0) | 6 (27.3) | 3 (13.0) | 6 (30.0) | 5 (45.5) | 12 (30.0) | 0 | 0 | 0 |
| 1 | 1 (8.3) | 17 (40.5) | 2 (40.0) | 8 (36.4) | 6 (26.1) | 9 (45.0) | 5 (45.5) | 27 (67.5) | 1 (4.8) | 1 (5.6) | 5 (55.6) |
| 2 | 2 (16.7) | 4 (9.5) | 0 | 7 (31.8) | 3 (13.0) | 3 (15.0) | 1 (9.1) | 1 (2.5) | 3 (14.3) | 2 (11.1) | 0 |
| 3 | 1 (8.3) | 0 | 0 | 1 (4.5) | 6 (26.1) | 2 (10.0) | 0 | 0 | 4 (19.0) | 6 (33.3) | 0 |
| ≥4 | 8 (66.7) | 1 (2.4) | 1 (20.0) | 0 | 5 (21.7) | 0 | 0 | 0 | 13 (61.9) | 9 (50.0) | 4 (44.4) |
Abbreviations: −, negative; +, positive; alt, altered; BC, breast cancer; DDR, DNA damage repair deficient; ECOG PS, Eastern Cooperative Oncology Group performance status; ERBB2, human epidermal growth factor receptor 2; HR, hormone receptor; mCRPC, metastatic castration-resistant prostate cancer; NA, not available; NSCLC, non–small-cell lung cancer; OC, ovarian cancer; PD-L1, programmed cell death 1 ligand 1; TNBC, triple-negative BC; TNM, tumor, node, metastasis; UC, urothelial carcinoma.
Included patients with ampullary cancer, BC, CRPC, colon cancer, mCRPC, metastatic prostate cancer, pancreatic adenocarcinoma, pancreatic cancer, and pulmonary malignant neuroendocrine carcinoma (1 patient each). The site of primary tumor was not reported for 1 patient.
Obtained from central laboratory tests.
Pending data or missing sample.
Derived from baseline tumor, circulating tumor DNA, and germline DDR alteration data.
Based on a loss of heterozygosity score greater than the predefined cutoff, 3 patients had DDR+ tumors at enrollment but were subsequently considered DDR− because of the lack of a loss of heterozygosity score following a change in assay specifications; 2 patients were enrolled based on a local test result but received negative results centrally.
Includes regimens in the neoadjuvant, adjuvant, or advanced or metastatic setting. In patients with BC, disease was considered as advanced or metastatic if disease progression occurred during previous neoadjuvant or adjuvant cytotoxic therapy or within 6 months of the last treatment dose.