Gocatamig + I-DXd for Small Cell Lung Cancer

Recruiting at 14 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antiretroviral therapy

Must not be taking: Immunosuppressive medications

Disqualifiers: Pulmonary compromise, Cardiovascular disease, Liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 44 months

138 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that ongoing treatment with immunosuppressive medications is not allowed, with some exceptions. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Gocatamig + I-DXd for Small Cell Lung Cancer?

Antibody-drug conjugates like trastuzumab deruxtecan have shown promising results in various cancers, including lung cancer, by effectively targeting and killing cancer cells. These drugs have demonstrated impressive response rates and survival outcomes in previously treated patients, suggesting potential effectiveness for small cell lung cancer as well. ^{1 2 3 4 5}

Is Gocatamig + I-DXd safe for humans?

Trastuzumab deruxtecan (T-DXd), similar to I-DXd, has been studied in various cancers and generally shows manageable safety, meaning side effects can be controlled. It has been used in breast and lung cancer patients with some success, but specific safety data for Gocatamig + I-DXd in small cell lung cancer is not available. ^{1 4 6 7 8}

What makes the drug Gocatamig + I-DXd unique for treating small cell lung cancer?

Gocatamig + I-DXd is unique because it combines a novel antibody-drug conjugate (ADC) approach, similar to trastuzumab deruxtecan (T-DXd), which has shown promise in targeting specific mutations in other cancers like non-small cell lung cancer. This approach allows for targeted delivery of chemotherapy directly to cancer cells, potentially improving effectiveness and reducing side effects compared to traditional chemotherapy. ^{3 7 9 10 11}

What is the purpose of this trial?

Researchers are looking for new ways to treat people with extensive-stage small cell lung cancer (SCLC) that has relapsed or is refractory. Gocatamig is a new type of immunotherapy that uses a person's immune system to find and destroy cancer cells. Ifinatamab deruxtecan (also known as I-DXd) is a drug which binds to a specific target on cancer cells and delivers treatment to destroy those cells. Researchers want to know if giving gocatamig and/or I-DXd can treat SCLC that did not respond or stopped responding to a prior treatment. The goals of this study are to learn: * If gocatamig and I-DXd are safe and well tolerated * If people who receive gocatamig and I-DXd have their SCLC get smaller or go away

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with extensive-stage small cell lung cancer (SCLC) that has come back or hasn't responded to treatment. They must have had platinum-based chemotherapy before and be able to give a tissue sample. People with HIV can join if their HIV is well controlled on medication.

Inclusion Criteria

My small cell lung cancer is in stage IV and has been treated with platinum-based chemotherapy before.

I have HIV and it is well controlled with medication.

I can provide a sample of my tumor tissue.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gocatamig and/or I-DXd at dosing intervals of Q2W or Q3W until disease progression or discontinuation criteria are met

Up to approximately 44 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gocatamig
• Ifinatamab Deruxtecan (I-DXd)

Trial Overview The study tests two drugs, Gocatamig and Ifinatamab Deruxtecan (I-DXd), in people whose SCLC has relapsed or is refractory. It aims to see if these treatments are safe and make the cancer smaller or disappear.

Participant Groups

Group I: Part 2 Arm 4: Gocatamig Monotherapy Experimental Treatment 1 Intervention

Participants in Japan will receive escalating doses of gocatamig until documented disease progression or discontinuation criteria are met.

Group II: Part 1 Arm 3b: Gocatamig and I-DXd Q2W Experimental Treatment 2 Interventions

Participants will receive gocatamig and I-DXd Q2W at the determined dose until documented disease progression or discontinuation criteria are met.

Group III: Part 1 Arm 3a: I-DXd Monotherapy Q2W Experimental Treatment 1 Intervention

Participants will receive I-DXd Q2W until documented disease progression or discontinuation criteria are met.

Group IV: Part 1 Arm 2: Gocatamig Q2W and I-DXd Q3W Experimental Treatment 2 Interventions

Participants will receive gocatamig Q2W and I-DXd Q3W at the determined dose until documented disease progression or discontinuation criteria are met.

Group V: Part 1 Arm 1: Gocatamig and I-DXd Q3W Experimental Treatment 2 Interventions

Participants will receive gocatamig and I-DXd Q3W at the determined dose until documented disease progression or discontinuation criteria are met.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Findings from Research

In a phase II study involving 152 patients with HER2-mutant metastatic non-small-cell lung cancer, trastuzumab deruxtecan (T-DXd) showed a confirmed objective response rate of 49% at 5.4 mg/kg and 56% at 6.4 mg/kg, indicating robust antitumor activity.

The safety profile of T-DXd was generally manageable, with fewer severe adverse events reported in the 5.4 mg/kg group compared to the 6.4 mg/kg group, suggesting that the lower dose may be preferable for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial. Goto, K., Goto, Y., Kubo, T., et al.[2023]

In a phase 1 trial involving 115 patients with HER2-positive breast cancer previously treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a manageable safety profile, with 59.5% of patients achieving a confirmed objective response.

Despite some serious treatment-emergent adverse events, including cases of interstitial lung disease and pneumonitis, the preliminary efficacy results suggest that trastuzumab deruxtecan is a promising treatment option, warranting further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Tamura, K., Tsurutani, J., Takahashi, S., et al.[2020]

Trastuzumab-deruxtecan (T-DXd) is a promising antibody-drug conjugate that shows clinically relevant activity in heavily pretreated patients with HER2-positive metastatic breast cancer, particularly those who have progressed on T-DM1.

While T-DXd demonstrates efficacy, it is important to monitor for interstitial lung disease, which occurred in about 13% of patients, highlighting the need for careful patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab-deruxtecan: an investigational agent for the treatment of HER2-positive breast cancer. Bartsch, R.[2022]

In a phase 1 trial involving 24 patients with advanced breast and gastric cancers, trastuzumab deruxtecan demonstrated promising antitumor activity, achieving a 43% objective response rate and 91% disease control rate, even in patients with low HER2 expression.

The study found that trastuzumab deruxtecan was well-tolerated, with no dose-limiting toxicities or significant cardiovascular effects reported, suggesting a maximum tolerated dose was not reached and indicating a favorable safety profile for further testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Doi, T., Shitara, K., Naito, Y., et al.[2018]

Antibody-drug conjugates (ADCs) are showing promising results in lung cancer treatment, with impressive response rates and survival outcomes in patients who have already undergone other treatments.

Current clinical trials are exploring various ADCs targeting different proteins in lung cancer, and novel strategies are being developed to enhance their safety and efficacy, such as increasing the drug-to-antibody ratio and using more potent payloads.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. Desai, A., Abdayem, P., Adjei, AA., et al.[2022]

In a real-world study of 143 patients with HER2+ metastatic breast cancer, trastuzumab deruxtecan (T-DXd) demonstrated a high overall response rate of 68% and a median progression-free survival of 16 months, confirming its efficacy in routine clinical practice.

The safety profile of T-DXd was consistent with previous studies, with 59% of patients experiencing any-grade toxicity, primarily nausea and neutropenia, but no new safety concerns were identified, indicating it is a well-tolerated treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study. Botticelli, A., Caputo, R., Scagnoli, S., et al.[2023]

In the DESTINY-Breast03 trial, trastuzumab deruxtecan (T-DXd) demonstrated superior progression-free survival and overall survival compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer, while maintaining quality of life (QoL) throughout treatment.

Patients receiving T-DXd experienced a median time to first hospitalization that was three times longer than those on T-DM1, indicating better overall health management and fewer hospital visits during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Curigliano, G., Dunton, K., Rosenlund, M., et al.[2023]

Trastuzumab deruxtecan (T-DXd) is a promising new antibody-drug conjugate that has been approved for treating HER2-positive metastatic breast cancer and gastric cancer, showing potential for use in other solid tumors as well.

T-DXd is expected to become the standard second-line treatment for HER2-positive metastatic breast cancer and may also benefit patients with hormone receptor-positive and triple-negative breast cancer that express low levels of HER2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond. Perez, J., Garrigós, L., Gion, M., et al.[2022]

The phase III DESTINY-Breast04 trial demonstrated that trastuzumab deruxtecan (T-DXd) is effective for patients with inoperable or metastatic HER2-low breast cancer, providing a new treatment option for this group.

Given the limited treatment options available for patients with HER2-low breast cancer, T-DXd is recommended as a new standard of care, highlighting its significance in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-DXd: New Standard for HER2-Low Breast Cancer. [2022]

References

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

Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial. [2023]

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

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. [2020]

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

Trastuzumab-deruxtecan: an investigational agent for the treatment of HER2-positive breast cancer. [2022]

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

Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. [2018]

5. Ireland pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Trastuzumab Deruxtecan in Patients With HER2+ Metastatic Breast Cancer: The DE-REAL Study. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Evolving Treatment Landscape of HER2-mutant Non-Small Cell Lung Cancer: Trastuzumab Deruxtecan and Beyond. [2023]

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

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. [2023]

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

Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond. [2022]

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

T-DXd: New Standard for HER2-Low Breast Cancer. [2022]

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

Efficacy with Trastuzumab Deruxtecan for Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutation in a Patient with a Poor Performance Status: A Case Report. [2021]