Table 5.
Response summary by genotype (combined across the 3 dose groups, N = 114)
| Endpoint or category | ATM | BRCA1/2 | CDK12 | NBN | PALB2 | RAD51B/Ca | SETD2 | Othersb |
|---|---|---|---|---|---|---|---|---|
| (n = 36) | (n = 42) | (n = 6) | (n = 5) | (n = 5) | (n = 6) | (n = 9) | (n = 5) | |
| Best response by RECIST v1.1, no. (%) | ||||||||
| cCR | 0 | 0 | 0 | 0 | 0 | 1 (16.7) | 0 | 0 |
| cPR | 3 (8.3) | 3 (7.1) | 0 | 0 | 0 | 0 | 1 (11.1) | 0 |
| uCR or uPR | 0 | 1 (2.4) | 0 | 0 | 0 | 1 (16.7) | 1 (11.2) | 0 |
| Overall response (RECIST only), no. (%) | 3 (8.3) | 4 (9.5) | 0 | 0 | 0 | 2 (33.3) | 2 (22.2) | 0 |
| Overall response (RECIST or tumor marker), no. (%) | 4 (11.1) | 4 (9.5) | 0 | 0 | 0 | 3 (50.0)c | 2 (22.2) | 0 |
| Clinical benefit rate,d no. (%) | 15 (41.7) | 14 (33.3) | 0 | 2 (40.0) | 1 (20.0) | 6 (100) | 4 (44.4) | 2 (40.0) |
| Mediane PFS, weeks | 17.7 | 12.6 | 11.6 | 12.1 | 7.0 | 45.5 | 18.0 | 7.0 |
| Mediane duration of treatment, weeks (min, max) | 11.1 (4.3, 112.3) | 11.8 (1.4, 93.7) | 6.4 (3.4, 13.7) | 12.4 (1.4, 31.7) | 5.7 (5.4, 22.3) | 52.8 (17.9, 117.1) | 13.4 (2.4, 78.0) | 5.7 (5.3, 33.4) |
| Median time to response, weeks (min, max) | 33.1 (29.9, 36.6) | 11.9 (6.1, 12.3) | – | – | – | 12.6 (6.1, 19.0) | 9.0 (6.0, 12.0) | – |
| Median duration of response,f weeks (min, max) | 24.3 (12.3, 36.3) | 36.0 (20.3, 74.4) | – | – | – | 36.0 (36.0, 36.0) | 23.1 (23.1, 23.1) | – |
| Molecular response (ctDNA reduction of 50% or more) | ||||||||
| Evaluable ctDNA for monitoring | 19 | 22 | 2 | 1 | 4 | 1 | 0 | 3 |
| Molecular response, n/m (%) | 5/19 (26.3) | 9/22 (40.9) | 0/2 (0) | 0/1 (0) | 2/4 (50.0) | 1/1 (100) | N/A | 0/3 (0) |
RAD51B (n = 2), RAD51C (n = 4). cCR = confirmed complete response; CI = confidence interval; cPR = confirmed partial response; ctDNA = circulating tumor DNA; m = no. evaluable ctDNA for monitoring; max = maximum; min = minimum; N/A = not applicable; PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumors; uCR = unconfirmed complete response; uPR = unconfirmed partial response.
Other genotypes include CHEK2 (n = 2) and RNASEH2 (n = 3).
All 3 patients with responses had RAD51C alterations.
Defined as overall response or duration of treatment of at least 16 weeks without progressive disease.
Kaplan–Meier method.
Applicable to patients with a cCR or cPR.