Extract:

The study, called TOPAZ-1, found that adding the immunotherapy drug durvalumab (Imfinzi) to standard chemotherapy modestly extended how long people with advanced biliary tract cancer lived. TOPAZ-1 is the first large clinical trial to show that initial, or first-line, treatment that includes immunotherapy can improve survival in patients with advanced biliary cancer.

Even a small improvement in survival is noteworthy, experts said, because the outlook for people with this fast-growing type of cancer is poor and treatment options are limited.In the trial, adding durvalumab to chemotherapy extended the length of time that people were still alive after starting treatment by a median of about 6 weeks compared with people who received chemotherapy plus a placebo. At 2 years after starting treatment on the trial, roughly 25% of patients who received chemotherapy plus durvalumab were still alive, compared with 10% of patients who received chemotherapy plus a placebo.

@James5656
Agree, this is terrific for IMU as I expect it will provide an ever glowing spotlight on the benefits of CF33 as a stand-alone treatment.
We know that IMU will be in frequent deep discussion with the FDA as they increase the bile duct cancer patients to 10 during 2024.
I hope the team is also actively taking to the Aus Federal Gov Health Minister and the TGA to get CF33 onto their radar.

@Harry58
Raise some valid concerns about the side effects of the treatment using using Durvalumab.
The side effects of Chemo are well documented and with Durvalumab used with chemo increases the possibility of severe side effects.

@pds1961

Agree. By comparison, the positive trial results for bile duct cancer IMU released on 6 Nov 2023 for their Phase 1 CF33 VAXINIA trial using CF33 alone (no chemo) is impressive and very promising:

"Notably one patient with bile duct cancer, treated IT with mid-dose level displayed pseudo progression (see below) with a 49% increase in tumour burden after two cycles of therapy. However, by the 4th cycle they achieved a Complete Response (iCR) with no known recurrence in over 200 days. A second patient with bile duct cancer, who previously progressed on prior drug therapies, achieved Stable Disease (SD) for > 4 months upon receiving IV-administered CF33-hNIS."

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The article also provides us with some potential patient numbers in the USA:

"Biliary tract cancer, which includes cancer of the bile ducts and gallbladder, is rare, with an estimated 11,980 new cases diagnosed in the United States in 2021. But the number of new cases being diagnosed worldwide each year is increasing, said Dr. Oh."

On the Ch7 news the cost of Durvalumab without Gov subsidy is around $120,000.

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About the TOPAZ-1 Study:

https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200015

Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer

Authors: Do-Youn Oh, M.D., Ph.D. [email protected], Aiwu Ruth He, M.D., Ph.D., Shukui Qin, M.D., Li-Tzong Chen, M.D., Ph.D., Takuji Okusaka, M.D., Ph.D., Arndt Vogel, M.D., Jin Won Kim, M.D., Ph.D., +22, for the TOPAZ-1 Investigators*Author Info & Affiliations

Published June 1, 2022

NEJM Evid 2022;1(8)

DOI: 10.1056/EVIDoa2200015

VOL. 1 NO. 8

• • ABSTRACT
  • INTRODUCTION
  • METHODS
  • RESULTS
  • DISCUSSION
  • NOTES
  • SUPPLEMENTARY MATERIAL
  • REFERENCES
• • Information & Authors
  • Metrics & Citations
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Abstract

BACKGROUND

Patients with advanced biliary tract cancer have a poor prognosis, and first-line standard of care (gemcitabine plus cisplatin) has remained unchanged for more than 10 years. The TOPAZ-1 trial evaluated durvalumab plus chemotherapy for patients with advanced biliary tract cancer.

METHODS

In this double-blind, placebo-controlled, phase 3 study, we randomly assigned patients with previously untreated unresectable or metastatic biliary tract cancer or with recurrent disease 1:1 to receive durvalumab or placebo in combination with gemcitabine plus cisplatin for up to eight cycles, followed by durvalumab or placebo monotherapy until disease progression or unacceptable toxicity. The primary objective was to assess overall survival. Secondary end points included progression-free survival, objective response rate, and safety.

RESULTS

Overall, 685 patients were randomly assigned to durvalumab (n=341) or placebo (n=344) with chemotherapy. As of data cutoff, 198 patients (58.1%) in the durvalumab group and 226 patients (65.7%) in the placebo group had died. The hazard ratio for overall survival was 0.80 (95% confidence interval [CI], 0.66 to 0.97; P=0.021). The estimated 24-month overall survival rate was 24.9% (95% CI, 17.9 to 32.5) for durvalumab and 10.4% (95% CI, 4.7 to 18.8) for placebo. The hazard ratio for progression-free survival was 0.75 (95% CI, 0.63 to 0.89; P=0.001). Objective response rates were 26.7% with durvalumab and 18.7% with placebo. The incidences of grade 3 or 4 adverse events were 75.7% and 77.8% with durvalumab and placebo, respectively.

CONCLUSIONS

Durvalumab plus chemotherapy significantly improved overall survival versus placebo plus chemotherapy and showed improvements versus placebo plus chemotherapy in prespecified secondary end points including progression-free survival and objective response rate. The safety profiles of the two treatment groups were similar. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03875235.)

GLTA