Durvalumab + Tremelimumab for Ovarian Cancer

Overseen By Ljiljana A. Miljevic

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants

Disqualifiers: Autoimmune disease, Organ transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two immunotherapy drugs, durvalumab and tremelimumab, for their effectiveness in treating ovarian, primary peritoneal, or fallopian tube cancer that has returned or isn't responding to other treatments. These drugs aim to help the body's immune system target and attack cancer cells. The trial explores whether administering these drugs together or sequentially is more effective. Participants who might be a good fit have these types of cancer that have stopped responding to platinum-based treatments and have measurable disease. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important findings.

Do I have to stop taking my current medications to join the trial?

The trial requires that you have not received any anti-cancer therapy within 28 days before starting the study drugs, and you must not use immunosuppressive medication within 28 days before the first dose, except for certain low-dose corticosteroids. If you're on other medications, the protocol does not specify, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining durvalumab and tremelimumab is generally safe for patients with various solid cancers. Studies have found that this combination has a manageable safety profile. Serious side effects can occur, but they are uncommon. For example, in some studies, about 8% of patients experienced severe reactions, with only a small number of deaths directly related to the treatment.

When administered sequentially, the safety of these drugs remains similar. Both durvalumab and tremelimumab are considered safe for cancer patients, with side effects comparable to those seen when used together.

While side effects are possible, the potential benefits in treating certain cancers often outweigh them. Prospective trial participants should discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of durvalumab and tremelimumab for ovarian cancer because these drugs work by harnessing the body's immune system to fight cancer, a method known as immunotherapy. Unlike traditional chemotherapy, which attacks cancer cells directly, these treatments target immune checkpoints like CTLA-4 and PD-L1, potentially leading to a more targeted immune response against the cancer. This approach could offer a new avenue of hope for patients, especially those who may not respond well to existing treatments like surgery and chemotherapy. Additionally, the combination therapy may enhance the effectiveness of the immune response compared to using either drug alone.

What evidence suggests that durvalumab and tremelimumab might be effective treatments for ovarian cancer?

Research shows that combining durvalumab and tremelimumab may help treat various cancers by enhancing the immune system's ability to attack tumors. In studies on other cancers, such as liver cancer, this combination has been linked to improved survival rates. These drugs work by blocking proteins that usually prevent the immune system from effectively fighting cancer cells. In this trial, participants will receive either a combination of tremelimumab and durvalumab or a sequential treatment of these drugs. While research on ovarian cancer continues, the drugs have shown promise in other cancers, suggesting potential benefits here as well. Early results indicate these drugs could slow the growth of cancer cells. ^{2 6 7 8 9}

Who Is on the Research Team?

Amir A. Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with recurrent or resistant ovarian, primary peritoneal, or fallopian tube cancer. Participants must be over 18 years old, have a good performance status (able to carry out daily activities), and have proper organ function. They should not be pregnant and must use effective birth control if of reproductive potential.

Inclusion Criteria

The informed consent must be written and signed by the subject prior to performing any protocol-related procedures, including screening evaluations.

My blood tests for organ function and bone marrow are within normal ranges.

I am willing and able to follow the study's requirements, including treatments, visits, and biopsies.

Exclusion Criteria

I have or had inflammatory bowel disease.

Your heart's electrical activity, measured by ECG, shows a prolonged QT interval.

I do not have any uncontrolled illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Sequential Arm)

Participants receive tremelimumab IV every 4 weeks for 4 cycles, followed by durvalumab IV every 4 weeks for up to 9 cycles upon progression

Up to 52 weeks

Treatment (Combination Arm)

Participants receive tremelimumab and durvalumab IV every 4 weeks for 4 cycles, followed by durvalumab IV every 4 weeks for up to 9 cycles

Up to 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 2 months

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Tremelimumab

Trial Overview

The study tests durvalumab and tremelimumab, two immunotherapy drugs that may help the immune system fight cancer. It's unclear if giving these drugs together or one after the other is more effective for treating certain gynecological cancers.

How Is the Trial Designed?

Group I: Arm II (combination tremelimumab, durvalumab) Experimental Treatment 2 Interventions

Patients receive tremelimumab IV and durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (sequential tremelimumab, durvalumab) Experimental Treatment 2 Interventions

Patients receive tremelimumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Upon progression, patients then receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity. This arm is closed to enrollment.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38009662/

Randomized phase 2 trial of tremelimumab and durvalumab ...

Patient-reported outcomes were similar in both arms. Conclusions: There was no difference in irPFS for combination tremelimumab plus durvalumab ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03026062

Study Details | NCT03026062 | Durvalumab and ...

This phase II trial studies how well durvalumab and tremelimumab work in treating participants with ovarian, primary peritoneal, or fallopian tube cancer

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0090825825001647

A phase I clinical trial of radiation therapy, durvalumab and ...

This phase I trial evaluated the safety/tolerability of combined RT and immunotherapy in metastatic gynecologic cancers.

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5569

Phase Ib INEOV neoadjuvant trial of durvalumab +

Results: 70 patients were randomized to Arm A (N=36) or Arm B (N=34). 4 pts were replaced for early toxicity and one early death attributed to ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10603354/

Phase II study of durvalumab and tremelimumab with front- ...

This study assessed the antitumor activity and safety of durvalumab plus tremelimumab combined with neoadjuvant chemotherapy (NAC) in patients newly diagnosed ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ...

Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2022/761289Orig1s000MultidisciplineR.pdf

761289Orig1s000 - accessdata.fda.gov

The data supporting FDA's assessment of the safety of tremelimumab in combination with durvalumab is based primarily on the HIMALAYA trial, a global ...

8.

imfinzihcp.com

imfinzihcp.com/hcc/unresectable/safety.html

Safety Profile of IMFINZI® (durvalumab) & IMJUDO® ...

Fatal adverse reactions occurred in 8% of patients who received IMFINZI and IMJUDO, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), ...

9.

onclive.com

onclive.com/view/neoadjuvant-durvalumab-tremelimumab-plus-chemo-meets-pfs-end-point-in-advanced-ovarian-cancer

Neoadjuvant Durvalumab/Tremelimumab Plus Chemo ...

According to the data, the study met its primary end point of PFS at 12 months of 63.6% (P = .021) and showed durable responses at a follow-up ...