Safety

DESTINY-Breast07: Safety (Results from Part 1 Module 2 [T-DXd + Pertuzumab] as of October 15, 2021 DCO)

Safety Overview
Dose Modification
Conclusions of Part 1 - Module 2 (T-DXd + pertuzumab)

Safety Overview

Safety Overview¹

Six patients were evaluable for DLTs (1 was not evaluable for DLTs due to using G-CSF for grade 3 neutropenia); no DLTs were reported
The combination treatment was generally well tolerated
There were no deaths; no patients experienced ILD/pneumonitis

Safety Results with the RP2D in Part 1/Module 2.

n (%)	Part 1/Module 2 T-DXd + pertuzumab N=7
Any AEs	7 (100)
Any grade ≥3 AEs Hematologic Neutrophil count decreased White blood cell count decreased Anemia Febrile neutropenia Platelet count decreased Non-hematologic Ejection fraction decreased Hypokalemia	3 (42.9) 2 (28.6) 2 (28.6) 1 (14.3) 1 (14.3) 1 (14.3) 1 (14.3) 1 (14.3)
Serious AEs	1 (14.3)^a
AEs leading to treatment discontinuation	1 (14.3)^b
AEs of special interest ILD/pneumonitis Left ventricular ejection fraction decreased	0 1 (14.3)^b
Deaths	0

^aFebrile neutropenia; ^bOne patient (14.3%) experienced a nonserious AE of grade 3 ejection fraction decreased; it was considered related to T-DXd but not to pertuzumab, led to discontinuation of T-DXd and pertuzumab, and was not resolved by the data cut‑off.

Dose Modification

Dose Modification¹

Dose Modifications in Part 1/Module 2.

	Patients, n (%)
Treatment	≥1 Dose delay	≥1 Dose reduction	≥1 Dose interruption
T-DXd	1 (14.3%) Reason: other^a	1 (14.3%) Reason: AE^b	0
Pertuzumab	0	Dose modifications not allowed per protocol	0

^aEvaluation for potential pneumonitis; ^bGrade 3 platelet count decreased.

Conclusions of Part 1 - Module 2 (T-DXd + pertuzumab)

Conclusions of Part 1 - Module 2 (T-DXd + pertuzumab)¹

The primary objective of part 1 of the ongoing DESTINY-Breast07 clinical trial was to assess safety and tolerability and determine the RP2D/recommended doses for expansion of T-DXd with anticancer therapies in patients with HER2+ breast cancer
Results reported are from the dose-finding stage and showed that T-DXd 5.4 mg/kg + pertuzumab 420mg Q3W was well tolerated in patients who received prior treatment in the metastatic setting
RP2D was T-DXd 5.4 mg/kg Q3W + pertuzumab 420mg Q3W (pertuzumab loading dose: 840 mg)

Abbreviations

AE = adverse event

;

DCO = data cut-off

;

DLT = dose limiting toxicity

;

G-CSF = granulocyte-colony stimulating factor

;

ILD = interstitial lung disease

;

Q3W = every three weeks

;

RP2D = recommended phase 2 dose

;

T-DXd = trastuzumab deruxtecan

References

1. André F, Hamilton EP, Loi S, et al. Dose-finding and -expansion studies of trastuzumab deruxtecan in combination with other anticancer agents in patients with advanced/metastatic HER2+ (DESTINY-Breast07) and HER2-low (DESTINY-Breast08) breast cancer [poster, supplement, and abstract]. Poster presented at: American Society of Clinical Oncology (ASCO) 2022 Congress; June 3-5, 2022; Chicago, IL. J Clin Oncol. 2022;40(suppl 16). Abs 3025.

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Document ID: 325e86bc-2a1f-401a-b8d6-fa304896a85b
Last updated: 14-February-2023

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