A Phase 2 Open-Label, Multi-Center Study of BMS-986504 as Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion

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Overview

Pumitamig (BNT327, formerly PM8002) is an investigational cancer drug being studied alone and with chemotherapy across several solid tumors. DB-1305 is not another name for pumitamig: it is a separate antibody–drug conjugate, also called BNT325, that has been studied in combination with BNT327. (biontechse.gcs-web.com)

Mechanism of action

Pumitamig is a bispecific antibody targeting PD-L1 and VEGF-A. It is designed to combine immune-checkpoint inhibition with blockade of VEGF-A signaling. (biontechse.gcs-web.com)

Efficacy

Human results are available, but the findings below are from early-phase studies; the response rates do not establish a benefit over standard treatment.

• Previously untreated advanced non-small-cell lung cancer: In the phase 2 portion of a global trial, pumitamig plus chemotherapy produced an objective response in 28 of 40 evaluable patients (70%); 21 of 40 (52.5%) responses were confirmed at the abstract’s data cutoff. Response-duration data were not yet mature. (asco.org)
• Cervical and platinum-resistant ovarian cancer: In a phase 1b/2a monotherapy study, objective responses were reported in 19 of 45 evaluable patients with cervical cancer (42.2%) and 7 of 34 with ovarian cancer (20.6%). (ascopubs.org)

Safety

In the lung-cancer combination trial, 19 of 43 patients (44.2%) had grade 3 or higher treatment-related adverse events; 8 (18.6%) had events considered related to pumitamig. Pumitamig-related events led to discontinuation in 2 patients (4.7%). In the cervical/ovarian monotherapy cohorts, 31 of 87 patients (35.6%) had grade 3 or higher treatment-related adverse events, and 13 (14.9%) discontinued treatment because of such events. Commonly reported events in those cohorts included protein in the urine and high blood pressure. These figures come from different studies and treatment regimens and should not be compared directly. (asco.org)

Further reading

• 2026 ASCO abstract: first-line non-small-cell lung cancer
• 2024 ASCO abstract: cervical and ovarian cancer

Last updated: Sep 2026

Overview

BMS-986504 (formerly MRTX1719) is an investigational oral drug being studied for advanced cancers with homozygous deletion of MTAP. Human results are available from an early-phase, nonrandomized trial; they do not yet establish how it compares with standard treatment. (pmc.ncbi.nlm.nih.gov)

Mechanism of action

Loss of MTAP causes methylthioadenosine (MTA) to accumulate in tumor cells. BMS-986504 is designed to bind and inhibit the PRMT5–MTA complex, exploiting this vulnerability while having less effect on cells without MTAP deletion. (pmc.ncbi.nlm.nih.gov)

Efficacy

In a phase 1/2 study of heavily pretreated patients with MTAP-deleted advanced solid tumors, the reported objective response rate was 23% and the disease control rate was 70% across evaluated tumor types. Median duration of response was 10.5 months. These figures come from an interim analysis, not a randomized comparison. (ascopubs.org)

A later analysis of the non–small cell lung cancer subgroup reported responses in 10 of 33 evaluable patients (30%). A separate analysis reported responses in 17% of 35 evaluable patients with pancreatic ductal adenocarcinoma; the small subgroups and differing analysis dates warrant caution when comparing rates. (sciencedirect.com)

Safety

In the 152-patient interim analysis, most treatment-related adverse events were grade 1 or 2; 13% of patients had a grade 3 or higher treatment-related event, and no grade 5 treatment-related events were reported. Longer follow-up and larger studies are needed to characterize safety more fully. (ascopubs.org)

Further reading

• Peer-reviewed preclinical study and early patient results
• 2025 phase 1/2 clinical-update abstract
• 2025 lung-cancer subgroup abstract

Last updated: Sep 2026

Overview

Daraxonrasib (RMC-6236; brand name Rasonque) is an oral cancer drug developed by Revolution Medicines. Although research into additional uses continues, it is no longer investigational for all uses: the US FDA approved it on August 26, 2026, for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. (fda.gov)

Mechanism of action

Daraxonrasib inhibits the active, GTP-bound form of RAS. It binds the cellular protein cyclophilin A; the resulting complex engages RAS and blocks downstream signaling. Its activity spans multiple mutant and wild-type RAS variants rather than a single mutation. (sciencedirect.com)

Efficacy

In the randomized phase 3 RASolute 302 trial, 500 patients with previously treated metastatic pancreatic cancer received daraxonrasib or the investigator’s choice of chemotherapy. Median overall survival was 13.2 versus 6.7 months in the full study population, and median progression-free survival was 7.2 versus 3.6 months, respectively. Objective response rates were 31.6% versus 11.2%. These results concern previously treated metastatic disease; they do not establish benefit in other settings. (pubmed.ncbi.nlm.nih.gov)

A separate early-phase study in previously treated RAS-mutant non-small-cell lung cancer reported tumor responses in more than 30% of patients. That use remains under study. (pubmed.ncbi.nlm.nih.gov)

Safety

In RASolute 302, adverse events of grade 3 or higher occurred in 61.8% of daraxonrasib recipients and 69.6% of chemotherapy recipients; treatment-related adverse events led to discontinuation in 1.2% and 11.2%, respectively. Earlier pancreatic-cancer trial results identified rash, diarrhea, nausea, mouth inflammation, vomiting and fatigue among treatment-related adverse events reported in at least 10% of patients. (pubmed.ncbi.nlm.nih.gov)

Further reading

• Phase 3 pancreatic-cancer trial, New England Journal of Medicine
• FDA approval announcement
• Daraxonrasib discovery and mechanism, Journal of Medicinal Chemistry

Last updated: Sep 2026

Overview

AMXT 1501 dicaprate is an investigational oral cancer drug studied primarily with difluoromethylornithine (DFMO, or eflornithine). Human results have been published from a phase I study in advanced solid tumors; they are preliminary and do not establish that the combination improves survival or outcomes compared with standard treatment. (doi.org)

Mechanism of action

AMXT 1501 inhibits cellular uptake of polyamines, molecules that support cell growth. DFMO inhibits ornithine decarboxylase, an enzyme involved in making polyamines. Combining the drugs is intended to limit both the production and import of polyamines by cancer cells. The precise polyamine transport target of AMXT 1501 has not been established in the clinical report. (doi.org)

Efficacy

In the phase I study, 56 heavily pretreated patients received AMXT 1501 alone briefly and/or with oral DFMO. The investigators reported two confirmed responses and 16 cases of stable disease, corresponding to a 6% overall response rate and 49% clinical benefit rate among patients assessed for response. Because this was an early-phase study without a comparison group, the results cannot establish how much benefit the combination provides. (doi.org)

Safety

The most common treatment-emergent adverse events were diarrhea (39.3%), nausea (37.5%), and vomiting (33.9%). The study reported no grade 4 or 5 treatment-emergent adverse events and no deaths attributed to them. (doi.org)

Further reading

• Phase I clinical study, ESMO Open (2025)
• Preclinical mechanism study, International Journal of Cancer (2013)

Last updated: Sep 2026

Inclusion Criteria:

* Participant must have histologically confirmed diagnosis of advanced and/or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene detected in tumor tissue.

* Depending on the cohort enrolled, participants must have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment (there must be no available treatment with curative intent or participant is ineligible or declines treatment) or be treatment-naïve with no prior systemic anticancer therapy for their unresectable or metastatic disease.

* Participant must have presence of at least one measurable tumor lesion per RECIST v1.1 or mRECIST at baseline.

* Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) must be ≤ 1.5 × ULN; subjects with liver metastasis or liver cancer must be ≤ 2 × ULN.

* Participant must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

* Participants must not have prior treatment with a PRMT5 or Methionine adenosyl transferase 2A (MAT2A) inhibitor.

* Participants must not have active brain metastases or carcinomatous meningitis. Participants are eligible if brain metastases are adequately treated, and participants are neurologically stable for at least 2 weeks prior to enrollment without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).

* Participants must not have history of gastrointestinal disease or other gastrointestinal conditions within 6 months prior to enrollment (including uncontrolled nausea, vomiting, malabsorption syndrome or non-gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess) likely to alter absorption of study treatment or result in inability to swallow oral medications.

* Participants must not have inadequate organ function, as determined by laboratory testing within the screening period.

* Participants must not have active viral HBV or HCV hepatitis.

* Other protocol defined inclusion/exclusion criteria applies.