DS-8201a + Olaparib for Endometrial Cancer

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Interstitial lung disease, Severe pulmonary compromise, Myocardial infarction, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 42 days

55 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take medications that are moderate or strong inhibitors or inducers of CYP3A, and if you are taking chloroquine or hydroxychloroquine, you will need a 14-day washout period (time without taking these medications) before joining the study.

What data supports the effectiveness of the drug Olaparib for treating endometrial cancer?

Olaparib has shown promising results in treating ovarian cancer, particularly in patients with BRCA mutations, and is approved for use in certain types of breast cancer. This suggests it may have potential benefits for other cancers, like endometrial cancer, that share similar genetic characteristics. ^{1 2 3 4 5}

Is the combination of DS-8201a and Olaparib safe for humans?

Olaparib (also known as Lynparza) has been studied for safety in various cancers, including ovarian and breast cancer. It is generally considered safe, but like all medications, it can have side effects, which may include nausea, fatigue, and anemia (low red blood cell count). There is limited specific safety data available for the combination of DS-8201a and Olaparib in endometrial cancer. ^{2 3 4 6 7}

What makes the drug combination of DS-8201a and Olaparib unique for treating endometrial cancer?

The combination of DS-8201a and Olaparib is unique because it pairs a novel antibody-drug conjugate (DS-8201a) with a PARP inhibitor (Olaparib), which is known for its effectiveness in treating cancers with DNA repair deficiencies, like BRCA mutations. This approach targets cancer cells more precisely and may offer a new treatment option for endometrial cancer, which currently lacks many targeted therapies. ^{1 2 7 8 9}

What is the purpose of this trial?

This trial tests the safety and best dose of two drugs, DS-8201a and olaparib, in patients with certain advanced cancers. DS-8201a targets and kills cancer cells with a specific protein, and olaparib stops cancer cells from fixing their DNA. The goal is to see if these drugs can shrink or control the cancer.

Research Team

Elizabeth Lee

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

This trial is for adults with HER2-expressing cancers that are advanced or can't be surgically removed, and specifically includes those with endometrial cancer. Participants must have tried at least one chemotherapy before, have a good performance status, and meet certain health criteria like normal organ function tests. Pregnant women, patients with recent heart attacks or uncontrolled infections, and those on certain drugs are excluded.

Inclusion Criteria

I have a preserved tissue sample for HER2 testing.

AST/ALT =< 3 x institutional ULN (within 14 days of randomization/enrollment)

INR/PT and aPTT =< 1.5 x ULN (within 14 days of randomization/enrollment)

Exclusion Criteria

You have experienced allergic reactions to similar drugs or compounds like DS-8201a, olaparib or monoclonal antibodies.

I have side effects from cancer treatment that haven't improved to mild or gone back to how they were before treatment.

I have or had lung inflammation that needed steroids, or it can't be ruled out by scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trastuzumab deruxtecan IV and olaparib PO in cycles of 21 days, with blood samples, ECHO or MUGA, and CT scans conducted throughout the trial

Up to 42 days

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days

Treatment Details

Interventions

• DS-8201a
• Olaparib

Trial Overview The trial is testing the combination of DS-8201a (an antibody-drug conjugate targeting HER2-positive tumor cells) and olaparib (a drug blocking enzymes involved in DNA repair), to see if they can shrink or stabilize these cancers. It's a phase I study to determine side effects and optimal dosages.

Participant Groups

Group I: Treatment (trastuzumab deruxtecan, olaparib) Experimental Treatment 7 Interventions

Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 and olaparib PO BID on days 1-21, days 8-14, or days 3-9 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients undergo collection of blood samples, ECHO or MUGA, CT, and biopsies throughout the trial.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Olaparib is a powerful inhibitor of PARP-1 and PARP-2, showing effectiveness in treating ovarian cancer, particularly in patients with germline BRCA mutations.

Phase III trials are currently evaluating olaparib's efficacy as a maintenance therapy after initial treatment in patients with BRCA mutations, highlighting its potential role in long-term cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Gunderson, CC., Moore, KN.[2016]

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]

The OPINION study is evaluating the safety and efficacy of olaparib as a maintenance therapy for women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer who do not have BRCA mutations, involving patients who have undergone at least two prior lines of platinum-based chemotherapy.

The primary goal of the study is to assess progression-free survival, which will help determine how effective olaparib is in delaying cancer progression in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. Poveda, AM., Davidson, R., Blakeley, C., et al.[2020]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

A 50-year-old woman with stage IVB poorly differentiated endometrial cancer experienced a significant clinical complete response after receiving the PARP inhibitor Olaparib, following the identification of a BRIP1 mutation.

This case represents the first documented instance of a pathologic complete response in high-grade endometrioid endometrial cancer treated with a PARP inhibitor, highlighting the potential for targeted therapies in cases with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Pathologic Response to PARP Inhibitor Olaparib in a Patient with Stage IVB Recurrent Endometrioid Endometrial Adenocarcinoma. Senguttuvan, RN., Wei, C., Raoof, M., et al.[2023]

Olaparib is an oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[2020]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

Olaparib is an effective treatment for patients with platinum-sensitive, relapsed BRCA-mutated high-grade serous ovarian cancer, showing significant improvement in progression-free survival compared to placebo in a study of 265 patients.

The treatment is generally well tolerated, with most side effects being mild to moderate, although fatigue, anemia, and neutropenia were noted as more severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. Frampton, JE.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. [2016]

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

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

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

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]

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

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. [2015]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Complete Pathologic Response to PARP Inhibitor Olaparib in a Patient with Stage IVB Recurrent Endometrioid Endometrial Adenocarcinoma. [2023]

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

Olaparib: first global approval. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

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

Olaparib: a review of its use as maintenance therapy in patients with ovarian cancer. [2016]