Newsflash
Prodotti competitors / Area Oncology

Breast Cancer competitive Updates (November 2023)

  • 10 novembre 2023 - Newsletter n. 43 - Novembre 2023
Immagine News
Attenzione! Il presente contenuto è disponibile solo in lingua originale.

Notable developments include:

  • HER2-expressing

RemeGen listed a new Phase 2 trial evaluating disitamab vedotin (RC48, HER2-ADC) ± toripalimab (Tuoyi, PD-1) in 2L+ chemo-naïve HR+/HER2-low mBC after prior ET

    • Primary outcome is PFS
    • Secondary outcomes include OS, ORR, DCR, DoR, AEs, and QoL measurements
    • All the trial sites listed are currently in China
    • Seagen and RemeGen entered into an exclusive worldwide licensing agreement for disitamab vedotin in Aug 2021
      • In March 2023, Pfizer and Seagen entered into a definitive merger agreement where Pfizer will acquire Seagen; the acquisition is expected to be completed in late 2023 or early 2024
      • Pfizer has noted plans to initiate further studies for disitamab vedotin in mBC

 

  • TNBC:

AstraZeneca and Daiichi Sankyo listed a new Phase 3 TROPION-breast04 trial evaluating neoadjuvant datopotamab deruxtecan (Dato-DXd; TROP2 ADC) + durvalumab (Imfinzi; anti-PD-L1) followed by adjuvant durvalumab +/- chemo vs neoadjuvant pembrolizumab (Keytruda; anti-PD-L1) + chemo followed by adjuvant pembrolizumab +/- chemo in 1L TNBC or HR-low/HER2- BC (N=1728; SSD: Nov 2023; PCD: Mar 2028; SCD: Aug 2030)

Highlights

  • The primary outcome measure is pCR and EFS; the secondary outcome measures include OS
  • Trial sites are listed across US, EU, and Asia
  • HR-low/HER2- has been explicitly added in addition to TNBC which may signify AZ’s intention to address the surfacing questions around the potential similarities in treatment outcomes of patients with low HR levels compared to TNBC patients
  • Dato-DXd: the posting of this trial marks the first Phase 3 trial evaluating neoadjuvant TROP2-ADC + IO followed by adjuvant IO
    • This is the second of the two P3 studies in TNBC disclosed by AZ during their post ESMO investor call to be posted; the other, TROPION-Breast05 (Dato-DXd + durva PD-L1+ (CPS≥10) locally recurrent inoperable or metastatic 1L TNBC) was posted on Oct 27, 2023

Additional Background

  • Dato-DXd is also being evaluated in the following pivotal trials:
  • Following the presentation of TROPION-Lung01 and TROPION-Breast01 results at ESMO’23, AZ confirmed that they have moved to file for Dato-DXd’s approval in both HR+/HER2- mBC and 2L+ mNSCLC, filing separately in the US and bundling these filings in the EU
  • Despite the lack of clarity around TROPION-Lung01 and its mixed results from ESMO’23, AZ did not provide a concrete answer on the Dato-DXd’s regulatory pathway or future label in 2L+ mNSCLC. However, AZ continuously highlighted the efficacy in non-squamous, confirming that AZ is hoping for approval in only the non-squamous population. Daiichi confirmed this in their Q3’23 earnings Q&A as well.
  • AZ previously stated in their ESMO’23 Investor Session that they would be limiting the number of squamous patients enrolled in 1L mNSCLC Dato-DXd trials due to the poor TROPION-Lung01 data in 2L+ squamous. Although AZ did not provide clarification here, Daiichi Sankyo mentioned in their Q3’23 earnings Q&A that they are stopping recruitment of squamous patients in TROPION-Lung08.
  • Though AZ appears to be moving forward with preparations for filings of Dato-DXd based on TROPION-Breast01PFS data from ESMO, mature OS data may still be required for approval
    • The P3 TROPION-Breast01 data presented at ESMO 2023 did not have significant OS data and was did not seem to significantly differentiate Dato-DXd from Trodelvy in TROPiCS-02; However, Dato-DXd remains a high threat as it could enter the HR+/HER2- mBC setting in an early line of treatment than Trodelvy’s current approval

 

  • HR+/HER2-

Pfizer

Pfizer listed a new Phase 3 trial evaluating PF-07220060 (CDK4i) + fulvestrant (SERD) vs investigator's choice of therapy (fulvestrant or everolimus + exemestane) in 1/2L HR+/HER2- mBC after prior CDK4/6i + ET in either 1L mBC or adjuvant setting (N=510; SSD: Dec 15, 2023; PCD: Nov 15, 2025; SCD: Nov 13, 2028)

  • Primary outcomes are PFS and OR
  • Secondary outcomes include OS, PFS, OR, DOR, CBR by BICR, AEs, and PK/PD measurements
  • the initiation of the Phase 3 trial was noted to be an oncology milestone in the company’s recent EC, ahead of the previously guided H1 2024 starting date
  • PF-07220060 will face competition form the current on-market CDK4/6is; however, it does not present a direct threat to Trodelvy at present

 

Pfizer listed a new Phase 1b/2 TACTIVE-U trial (Sub-Study C) evaluating vepdegestrant (oral PROTAC) + samuraciclib (CDK7i) in 1-3L HR+/HER2- mBC after prior CDK4/6i therapy (N=67; SSD: Nov 10, 2023; PCD: Aug 3, 2026; SCD: Feb 2, 2027)

  • Primary outcome measures include dose limiting toxicities (P1b) and OR by investigator assessment (P2)
  • Secondary outcome measures include DoR, CBR, PFS and OS
  • vepdegestrant is also being investigated the following Phase 3 trials and being messaged for being a “next-generation endocrine therapy backbone”:
    • Phase 3 VERITAC-3 trial evaluating vepdegestrant + palbociclib in 1L ER+/HER2- mBC
    • Phase 3 VERITAC-2 trial evaluating vepdegestrant in 2L+ ER+/HER2- mBC

 

Roche

Roche updated the Phase 3 pionERA trial evaluating giredestrant (oral SERD) + CDK4/6i vs fulvestrant (SERD) + CDK4/6i in 1L ER+/HER2- mBC with resistance to prior adjuvant ET

  • The overall status was updated from “not yet recruiting” to “recruiting”
  • The SSD was delayed from Oct 31, 2023 to Nov 24, 2023
  • giredestrant is currently being assessed in the following registrational trials 
    • Phase 3 IidERA trial of adjuvant giredestrant in ER+/HER2- eBC 
    • Phase 3 persevERA trial of giredestrant + palbociclib (Ibrance, CDK4/6i) in 1L ER+/HER2- mBC 
    • Phase 3 evERA trial of giredestrant + everolimus (mTOR inhibitor) in 1L+ ER+/HER2- mBC after CDK4/6i + ET

 

Roche updated the Phase 2/3 INAVO120 trial evaluating inavolisib (PI3Kα inhibitor) + palbociclib (Ibrance; CDK 4/6 inhibitor) + fulvestrant (SERD) vs placebo + palbociclib + fulvestrant in 1L PIK3CAmut HR+/HER2- BC

  • The PCD was pushed forward from Nov 30, 2025 to Sep 29, 2023
  • data readout for the INAVO120 trial has recently been pulled forward into Q4 2023 with Roche commenting that it could potentially be the first positive Phase 3 readout for inavolisib
  • The INAVO120 trial has the potential to move PI3K inhibitors into early lines of therapy
    • Novatis’s alpelisib (Piqray) is the only on-market PI3K inhibitor in BC being approved in 2L PIK3CAmut HR+/HER2- mBC
    • Inavolisib or alpelisib are currently limited threat to Trodelvy

 

  • General BC

Merck kGaA announced a strategic collaboration with Jiangsu Hengrui Pharmaceuticals for next-generation selective PARP1 inhibitor and ADCs

  • The partnership includes an exclusive license worldwide (ex-China) to develop, manufacture and commercialize Hengrui’s HRS-1167 (PARP1 inhibitor) and SHR-A1904 (Claudin-18.2 ADC)
    • In addition, Merck will have the option to co-promote both assets in China
  • SHR-A1904 was highlighted to complement Merck’s internal preclinical and clinical ADC portfolio applying different linker payload technologies
    • The asset is currently being evaluated in multiple Phase 1/2 trials in advanced solid tumors
      • It is unclear whether BC patients were included; nevertheless, given the early stage of development, SHR-A1904 will unlikely have significant impact on Trodelvy in the immediate future

Pfizer

Pfizer withdrew the Phase 1 basket trial evaluating PF-07224826 (CDK2/4/6i) that included a BC cohort

  • The decision was based on business considerations and not due to specific safety reasons or request from a regulatory authority
Tags:
Grazie per il tuo feedback!