Gocatamig + I-DXd for Small Cell Lung Cancer

Recruiting at 40 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

242 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks new treatments for individuals with extensive-stage small cell lung cancer (SCLC) that has recurred or stopped responding to previous treatments. The trial tests combinations of two new drugs, gocatamig and Ifinatamab Deruxtecan (I-DXd), with durvalumab to determine if they can safely shrink or eliminate the cancer. Participants with SCLC who previously received platinum-based chemotherapy without success might be suitable candidates. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works and measure its effectiveness in an initial group, offering participants access to potentially groundbreaking therapies.

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.

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

Research has shown that using gocatamig and I-DXd together generally maintains a manageable safety profile. In earlier studies, some patients experienced side effects, but most were mild. Gocatamig alone has been found safe and shows promise in treating small cell lung cancer (SCLC).

I-DXd has also been tested independently and is generally safe. Some patients reported side effects like interstitial lung disease or pneumonitis, but these were mostly mild. Severe reactions occurred in a few patients, but these were rare.

The combination of gocatamig with durvalumab, another type of immunotherapy, is still under study for safety, and details remain unclear. However, both drugs have been used successfully in treating other cancers.

Overall, these treatments are being carefully studied in trials to ensure safety and effectiveness for patients with SCLC. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments Gocatamig and Ifinatamab Deruxtecan (I-DXd) for small cell lung cancer because they offer new ways to tackle this tough-to-treat cancer. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, I-DXd is an antibody-drug conjugate that specifically targets cancer cells, potentially reducing harm to healthy cells. Gocatamig, on the other hand, is a novel compound that may work synergistically with I-DXd or other drugs to enhance their effectiveness. Additionally, some arms of the trial explore Gocatamig in combination with durvalumab, an immunotherapy, which could further boost the immune system’s ability to fight cancer. These innovative approaches aim to improve outcomes and reduce side effects for patients with small cell lung cancer.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

Research has shown promising results for treating extensive-stage small cell lung cancer (SCLC) that has recurred or is unresponsive to treatment. Ifinatamab deruxtecan (I-DXd), which participants in this trial may receive as monotherapy, has demonstrated significant response rates in patients with this type of SCLC. In earlier studies, many patients treated with I-DXd experienced a reduction in cancer size or complete disappearance. Gocatamig, another treatment option in this trial, is an immunotherapy that aids the immune system in identifying and destroying cancer cells. Early data for gocatamig in SCLC shows a response rate of 37%, indicating that 37% of patients saw their cancer shrink or disappear. This trial will also explore the combination of gocatamig and I-DXd to enhance effectiveness by using both treatments together. ^{1 3 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Part 3 Arm 7: Gocatamig and Durvalumab Experimental Treatment 2 Interventions

Participants will receive gocatamig and durvalumab at a determined dose until documented disease progression or discontinuation criteria are met.

Group II: Part 2 Arm 6: Gocatamig Experimental Treatment 1 Intervention

Participants will receive gocatamig at a determined dose until documented disease progression or discontinuation criteria are met.

Group III: Part 2 Arm 5: Gocatamig Monotherapy in China Experimental Treatment 1 Intervention

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

Group IV: Part 2 Arm 4: Gocatamig Monotherapy in Japan Experimental Treatment 1 Intervention

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

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

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

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

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

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

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

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

Participants will receive gocatamig and I-DXd at a 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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06780137

NCT06780137 | A Study to Evaluate the Safety and ... This study will consist of two parts. Part 1 will assess the safety, tolerability, and efficacy of gocatamig and I-DXd at doses determined in study MK-6070-001.

2. msdclinicaltrials.com msdclinicaltrials.com/trial/nct06780137/

A Study to Evaluate the Safety and Efficacy of MK-6070 and ... 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 ...

3. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/documents/d/datahub/wclc-2025_i-dxd_johnson_poster-final

A phase 1b/2 study of gocatamig and ... proteins highly expressed on the surface of small cell lung cancer (SCLC) cells1,2. • Gocatamig (MK-6070, HPN328) is a DLL3- directed T-cell ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/568557

A Study to Evaluate the Safety and Efficacy of Gocatamig ... 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12485632/

What Is On the Horizon for the Diagnosis and Treatment of ... Another study investigating the efficacy of durvalumab combined with olaparib in patients with relapsed SCLC reported a similar outcome, with an ORR of 10.5% ...

6. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/documents/d/datahub/esmo-2025_i-dxd_bar_poster_final

A phase 1b/2 study of gocatamig and ... • Part 3: Evaluate the safety and tolerability of gocatamig in combination with durvalumab ... on the surface of small cell lung cancer (SCLC) ...

7. daiichisankyo.us daiichisankyo.us/press-releases/-/article/daiichi-sankyo-continues-to-transform-standards-of-care-for-patients-with-three-landmark-breast-cancer-trials-and-additional-data-across-industry-leading-adc-portfolio-at-esmo

Press Releases Updated results from a phase 1/2 study of gocatamig for small cell lung cancer and other neuroendocrine cancers ... small cell lung cancer: ...

8. withpower.com withpower.com/trial/phase-2-lung-neoplasms-1-2025-8b780

Gocatamig + I-DXd for Small Cell Lung Cancer 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 ...