Olaparib + Durvalumab for Solid Tumors

(SOLID Trial)

Recruiting in Toronto (>99 mi)

Overseen By Eric Chen, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: CYP3A inducers, Immunosuppressants

Disqualifiers: Other malignancy, Uncontrolled infection, Autoimmune, 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: 10

Duration: 3 years

58 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 2 study of the combination of drugs olaparib and durvalumab for the treatment of isocitrate dehydrogenase or (IDH) mutated solid tumors. The purpose of this study is to assess the efficacy of the drug combination via overall response rate and overall disease control rate. It is believed that giving olaparib and durvalumab together would be more useful when given to patients with IDH-mutated solid tumors than giving each drug alone.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for known strong or moderate CYP3A inducers before starting olaparib, which is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. This does not apply to patients in Cohort A. If you are taking these medications, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug combination of olaparib and durvalumab for solid tumors?

Research shows that the combination of olaparib and durvalumab has shown antitumor activity in preclinical studies and increased response rates in breast cancer treatment. Additionally, durvalumab alone has demonstrated effectiveness in treating various solid tumors, including non-small-cell lung cancer. ^{1 2 3 4 5}

Is the combination of Olaparib and Durvalumab safe for humans?

Studies have shown that the combination of Olaparib and Durvalumab is generally safe, with no dose-limiting toxicities reported. Some side effects like fatigue and high blood pressure were noted, but the treatment was considered tolerable. ^{1 2 4 6 7}

What makes the drug combination of Olaparib and Durvalumab unique for treating solid tumors?

The combination of Olaparib, a PARP inhibitor that targets cancer cells with DNA repair issues, and Durvalumab, an immunotherapy drug that helps the immune system attack cancer cells, is unique because it combines two different mechanisms to enhance anti-tumor activity, potentially offering a more effective treatment for certain solid tumors compared to standard therapies. ^{2 6 8 9 10}

Research Team

Eric Chen, M.D.

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

Adults with IDH-mutated solid tumors, including specific brain and bile duct cancers, who have undergone limited prior treatments can join this trial. They must be in good physical condition (ECOG 0-1), not pregnant, willing to prevent pregnancy, and able to swallow pills. Participants should have a life expectancy of at least 16 weeks and stable health without recent major surgeries or uncontrolled medical issues.

Inclusion Criteria

My brain tumor is IDH mutant and I've had no more than 2 treatments after it first came back.

I am 18 years old or older.

I have a brain tumor or cancer spread to the brain, feel fine, and it's been 4 weeks since my last brain treatment.

Exclusion Criteria

I do not have any serious, uncontrolled health issues or infections.

I have lasting side effects from cancer treatment, but not hair loss or blood test issues.

I cannot swallow pills or have stomach issues affecting medication absorption.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive Olaparib orally twice a day and Durvalumab intravenously on Day 1 of every 28-day cycle

3 years

Monthly visits (in-person)

End of Study Drug Visit

Participants undergo tests and procedures for safety and research purposes after the last dose of study drugs

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored by telephone or clinic visit every 8-12 weeks until they no longer wish to be followed or start a new anti-cancer treatment, or until 1 year after last dose of study drugs

1 year

Every 8-12 weeks (in-person or virtual)

Treatment Details

Interventions

• Durvalumab
• Olaparib

Trial Overview The study is testing the combination of two drugs: Olaparib and Durvalumab for treating IDH-mutated solid tumors. The goal is to see if taking these drugs together works better than when they're taken separately by measuring how well the cancer responds and how long patients' diseases are controlled.

Participant Groups

Group I: Cohort B: IDH mutated cholangiocarcinoma Experimental Treatment 2 Interventions

Olaparib, by mouth (orally), twice a day, every day. Durvalumab, by vein (intravenously), on Day 1 of every 28 day cycle.

Group II: Cohort A: IDH mutated glioma Experimental Treatment 2 Interventions

Olaparib, by mouth (orally), twice a day, every day. Durvalumab, by vein (intravenously), on Day 1 of every 28 day cycle.

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?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In a study involving 34 patients with BRCA1 or BRCA2 mutated metastatic breast cancer, the combination of olaparib and durvalumab demonstrated promising antitumor activity, with 80% of patients showing disease control at 12 weeks.

The treatment was generally safe, with 32% of patients experiencing grade 3 or worse adverse events, but no treatment-related deaths were reported, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Domchek, SM., Postel-Vinay, S., Im, SA., et al.[2021]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

The combination of olaparib and durvalumab (O+D) showed a progression-free survival rate of 35% at 6 months in patients with advanced solid tumors, including rare cancers with homologous recombination repair (HRR) defects, indicating its efficacy in this challenging patient population.

O+D was found to be safe, with only 6% of patients experiencing serious adverse events, and it produced durable objective tumor responses in several rare cancer types, suggesting it could be a promising treatment option without new toxicity concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations. Thavaneswaran, S., Kansara, M., Lin, F., et al.[2023]

The I-SPY2 platform-based phase II studies have shown that combining durvalumab and olaparib with standard neoadjuvant chemotherapy significantly improves the pathological complete response rate in patients with HER2-negative breast cancer.

This treatment approach is effective regardless of the hormone receptor status, suggesting a broad applicability for these therapies in this specific breast cancer population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

I-SPY2 platform: New lessons from the olaparib and durvalumab combination in breast cancer treatment. Perez-Garcia, J., Gion, M., Cortes, J.[2021]

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

In a phase I study involving 26 women with recurrent cancers, the combination of the PD-L1 inhibitor durvalumab with olaparib or cediranib was found to be tolerable and showed promising anti-tumor activity, with an 83% disease control rate for the durvalumab plus olaparib group.

The recommended phase II doses were established as durvalumab 1,500 mg every 4 weeks with olaparib 300 mg twice daily, or cediranib 20 mg on an intermittent schedule, indicating that these combinations could be viable options for further investigation in treating recurrent women's cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of the Programmed Death-Ligand 1 Inhibitor Durvalumab in Combination With Poly (ADP-Ribose) Polymerase Inhibitor Olaparib or Vascular Endothelial Growth Factor Receptor 1-3 Inhibitor Cediranib in Women's Cancers: A Dose-Escalation, Phase I Study. Lee, JM., Cimino-Mathews, A., Peer, CJ., et al.[2022]

The combination of durvalumab (a PD-L1 inhibitor) and olaparib (a PARP inhibitor) with standard paclitaxel chemotherapy significantly increased pathologic complete response (pCR) rates in stage II/III HER2-negative breast cancer, with rates rising from 20% to 37% overall.

While DOP showed enhanced efficacy, particularly in high-risk hormone receptor-positive/HER2-negative patients (pCR 64% vs. 22%), it also resulted in a higher incidence of immune-related grade 3 adverse events (12.3% vs. 1.3% in the control group).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. Pusztai, L., Yau, C., Wolf, DM., et al.[2023]

The combination of olaparib, cediranib, and durvalumab was found to be tolerable in a phase 1 study involving 9 patients with recurrent women's cancers, with no dose-limiting toxicities reported.

The treatment showed promising preliminary efficacy, with a 67% clinical benefit rate, including partial responses in 44% of patients, indicating potential for further investigation in a phase 2 study for recurrent ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1-3 inhibitor, cediranib, in recurrent women's cancers with biomarker analyses. Zimmer, AS., Nichols, E., Cimino-Mathews, A., et al.[2023]

In a phase I study involving 12 patients with advanced solid tumors, the combination of olaparib and bevacizumab was found to be generally well tolerated, with no dose-limiting toxicities reported.

The most common side effects were mild nausea and fatigue, indicating that the treatment has an acceptable safety profile, making it a candidate for further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours. Dean, E., Middleton, MR., Pwint, T., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

4. England pubmed.ncbi.nlm.nih.gov

A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

I-SPY2 platform: New lessons from the olaparib and durvalumab combination in breast cancer treatment. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of the Programmed Death-Ligand 1 Inhibitor Durvalumab in Combination With Poly (ADP-Ribose) Polymerase Inhibitor Olaparib or Vascular Endothelial Growth Factor Receptor 1-3 Inhibitor Cediranib in Women's Cancers: A Dose-Escalation, Phase I Study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. [2023]

9. England pubmed.ncbi.nlm.nih.gov

A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1-3 inhibitor, cediranib, in recurrent women's cancers with biomarker analyses. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours. [2023]