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R. Jotte
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-002 - G1T28, a Cyclin Dependent Kinase 4/6 Inhibitor, in Combination with Topotecan for Previously Treated Small Cell Lung Cancer: Preliminary Results (ID 5213)
14:30 - 15:45 | Author(s): R. Jotte
- Abstract
Background:
Chemotherapy-induced bone marrow and immune system toxicity causes significant acute and long-term consequences. G1T28 is a potent and selective CDK4/6 inhibitor (CDK4/6i) in development to reduce chemotherapy-induced myelosuppression and preserve immune system function in small cell lung cancer (SCLC) patients. Hematopoietic stem and progenitor cells (HSPC) are dependent upon CDK4/6 for proliferation, and preclinical models demonstrated that transient G1T28-induced G~1~ cell cycle arrest renders them resistant to chemotherapy cytotoxicity, allowing faster hematopoietic recovery, preservation of long-term stem cell and immune system function, and enhancement of chemotherapy anti-tumor activity.
Methods:
Objectives of this ongoing multicenter Phase 1b/2a study are to assess the dose limiting toxicities (DLTs), safety, hematological profile, PK, and anti-tumor activity of G1T28 in combination with topotecan (NCT02514447). The study consists of a limited open-label, dose-finding portion (Part 1; up to 40 patients), and an open‑label, single-arm expansion portion (Part 2; 28 patients). Eligible patients had histologically/cytologically confirmed SCLC, adequate organ function, ECOG performance status 0-2, 1-2 prior lines of chemotherapy, and no symptomatic brain metastases. G1T28, at a starting dose of 200 mg/m[2] (derived from the Phase 1a healthy volunteer study and expected to maintain HSPC G1 arrest beyond topotecan exposure), was administered IV prior to IV topotecan on days 1-5 every 21-days.
Results:
21 patients (median age 68, 5 females, 20 white and 1 African-American) have been enrolled across 5 cohorts. DLTs due to Grade 3/4 myelotoxicity occurred in the first two cohorts and were associated with supra-therapeutic topotecan exposures due to decreased topotecan clearance by G1T28. Reducing the topotecan dose achieved exposures in the therapeutic range and was well tolerated. No episodes of febrile neutropenia or bleeding have occurred to date. For the 17 evaluable patients, there were 5 PR, 8 SD, and 4 PD. In the 6 platinum refractory patients there were 1 PR, 3 SD, and 2 PD.
Conclusion:
G1T28, a novel CDK4/6i, combined with topotecan for previously treated SCLC patients has been well tolerated, without any episodes of febrile neutropenia or bleeding. There are encouraging early signs of anti-tumor activity, with a response rate of 29% overall (36%, 4/11 in sensitive and 17%, 1/6 in refractory) and a clinical benefit rate (CR+PR+SD) of 76% overall (82%, 9/11 in sensitive and 67%, 4/6 in refractory). This novel approach, allowing the administration of chemotherapy with preservation of hematopoietic function and cellular immunity, could potentially improve treatment outcomes of patients with CDK4/6-independent tumors. Updated data will be presented.
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-072 - Interim Results from ABOUND.Sqm: Safety of nab-Paclitaxel/Carboplatin Induction Therapy in Squamous (SCC) NSCLC (ID 4391)
14:30 - 15:45 | Author(s): R. Jotte
- Abstract
Background:
Improving tolerability of chemotherapy for patients with SCC NSCLC remains an important aspect of care. Induction therapy with nab-paclitaxel/carboplatin followed by nab-paclitaxel maintenance therapy could be an effective treatment option for this patient population. Interim safety results from the induction part of the ongoing ABOUND.sqm study are reported here.
Methods:
Patients with advanced SCC NSCLC who had no prior chemotherapy for metastatic disease received induction therapy with nab-paclitaxel 100 mg/m[2] on days 1, 8, and 15 + carboplatin AUC 6 on day 1 (21-day cycles) for 4 cycles. Patients not progressing after 4 cycles were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m[2] on days 1 and 8 of each 21-day cycle + best supportive care (BSC) or BSC alone until progression/unacceptable toxicity. Progression-free survival from randomization into the maintenance part of the study is the primary endpoint. Secondary endpoints include safety (analyzed as treatment-emergent adverse events [TEAEs], overall survival, overall response rate, and disease control rate.
Results:
212 patients receiving induction treatment were evaluable in this analysis. Median age was 68 years; 66% of patients were male, 87% were white, and 99% had an Eastern Cooperative Oncology Group performance status of 0-1. Discontinuations were observed in 94/212 patients (44%) during induction. Of these, 35/94 (37%) discontinued due to disease progression, 23/94 (24%) due to AEs, 11/94 (12%) due to other reasons, 10/94 (11%) due to death, 9/94 (10%) due to patient decision, and 6/94 (6%) due to symptomatic deterioration. The median percentage of per-protocol dose of nab-paclitaxel was 75%, and median dose intensity was 74.87 mg/m[2]/week. At least 1 nab-paclitaxel dose reduction, missed dose, or dose delay occurred in 41%, 51%, and 58% of treated patients, respectively. Grade 3/4 TEAEs were mainly hematologic and included neutropenia (86/212; 41%), anemia (52/212; 25%), and thrombocytopenia (33/212; 16%). Grade 3/4 peripheral neuropathy occurred in 8/212 patients (4%).
Conclusion:
This interim report from the ABOUND.sqm study demonstrates that the tolerability profile of nab-paclitaxel/carboplatin was consistent with that reported in the phase III study, and no new safety signals were observed. Updated results will be presented at the meeting. NCT02027428
