KEYLYNK-009: A phase II/III, open-label, randomized study of pembrolizumab (pembro) plus olaparib vs pembro plus chemotherapy after induction with first-line pembro plus chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC).

Abstract

TPS596 Background: Combination therapy with immunotherapy + chemotherapy is a promising approach for first-line (1L) treatment of locally recurrent, inoperable TNBC or metastatic TNBC (mTNBC). However, an unmet need exists for effective and tolerable maintenance regimens in mTNBC to sustain clinical benefit after induction therapy and avoid potential toxicity or resistance in response to prolonged chemotherapy. The PARP inhibitor olaparib has demonstrated efficacy in the maintenance setting for multiple platinum-sensitive tumors, and the prevalence of BRCA mutations in TNBC may make these tumors particularly sensitive to DNA-damaging agents. Moreover, previous data suggest that combination therapy with olaparib and the PD-1 inhibitor pembro may have clinical benefits. KEYLYNK-009 (NCT04191135) is a phase II/III, open-label, randomized study of pembro + olaparib or pembro + chemotherapy after induction with 1L pembro + chemotherapy in patients with locally recurrent, inoperable TNBC or mTNBC. Methods: This 2-in-1 study design will enroll ~317 patients in phase II; if a planned efficacy boundary is met, ~615 additional patients will be enrolled in phase III. Patients eligible for induction therapy must have measurable, locally recurrent, inoperable TNBC that cannot be treated with curative intent or mTNBC previously untreated with chemotherapy in the metastatic setting. All patients will receive up to 6 cycles of induction therapy with pembro 200 mg every 3 wk (Q3W) + chemotherapy (carboplatin AUC 2 + gemcitabine 1000 mg/m2). Patients eligible for postinduction treatment must achieve complete or partial response or maintain stable disease during induction after 4-6 treatment cycles, with ECOG PS 0/1 and no grade >1 toxicities related to induction therapy (excluding alopecia, Hb ≥9.0 g/dL, grade 2 hyper-/hypothyroidism, or grade 2 hyperglycemia). These patients will be randomized 1:1 to receive pembro 200 mg Q3W + olaparib 300 mg twice daily or continue pembro + chemotherapy (same as induction regimen). Olaparib and chemotherapy may continue until progression or unacceptable toxicity; pembro may continue for ≤35 cycles (including induction), unacceptable toxicity, or progression. Phase III dual primary endpoints are PFS per RECIST v1.1 by BICR and OS. Secondary endpoints include OS and PFS in patients with BRCAm, health-related quality of life, and safety. Enrollment is ongoing. Clinical trial information: NCT04191135 .