Oncology Today—December 8, 2025

This week’s oncology roundup covers major advances in targeted therapy, immuno-oncology, diagnostics, and trial innovation shaping cancer care.

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🧬 Gintemetostat in triple-class refractory myeloma [1] [US • ASH 2025]

https://www.targetedonc.com/view/gintemetostat-shows-early-promise-in-relapsed-refractory-myeloma

Context: Phase 1 dose-escalation of oral MMSET/NSD2 inhibitor KTX-1001 in heavily pretreated, triple-class refractory R/R myeloma, including high-risk t(4;14).

Key point: Among 40 patients, single-agent gintemetostat produced 1 VGPR, 1 PR, 2 MR, 12 SD, with 75% TEAEs and 45% grade ≥3 events but no new safety signals.

Implication: Validates MMSET/NSD2 as a druggable epigenetic target and sets up combination studies with PIs, IMiDs, and CELMoDs in refractory disease.

💉 Takeda–Innovent ADC/immuno-oncology alliance closes [2] [Global • 24 Oct–Dec 2025]

https://www.europeanpharmaceuticalreview.com/news/268636/takeda-innovent-adc-immuno-oncology-deal-closing/

Context: Global deal (up to $11.4B) gives Takeda rights to IBI363 (PD-1/IL-2α-bias), IBI343 (CLDN18.2 ADC), plus option on IBI3001 (EGFR/B7-H3 ADC).

Key point: $1.2B upfront and ex-Greater China rights position Takeda with multiple next-gen assets across NSCLC, CRC, gastric, and pancreatic cancers.

Implication: Increases CLDN18.2 and multi-target ADC competition and may reshape global partnering dynamics for Chinese biotech pipelines.

🩸 Astrin’s Certitude™ non-imaging breast test [3] [US • 3 Dec 2025]

https://uk.finance.yahoo.com/news/astrin-biosciences-launches-certitude-breast-154200645.html

Context: Deep-proteomics + AI blood test for early breast cancer detection, aimed especially at women with dense breast tissue.

Key point: In 1,242 women, Certitude achieved 92% sensitivity, 93% specificity and >99.9% NPV across stages and subtypes; US launch targeted for early 2026.

Implication: Could become a major adjunct to mammography, reducing false-positive imaging and biopsies, and opening a new AI-driven screening segment.

🧪 Natera acquires Foresight Diagnostics (PhasED-Seq MRD) [4] [US • 5 Dec 2025]

https://www.contractpharma.com/breaking-news/natera-acquires-foresight-diagnostics/

Context: All-stock transaction: $275M upfront plus $175M in revenue/reimbursement milestones.

Key point: Adds PhasED-Seq ctDNA MRD with LOD95 ~0.3 ppm and sub-0.1 ppm detection, reinforcing Natera’s leadership in lymphoma and solid-tumor MRD.

Implication: Raises the competitive bar on assay sensitivity and may accelerate MRD adoption as a regulatory-grade endpoint in hematologic malignancies.

🏥 Paradigm Health acquires Flatiron clinical research business [5] [US • 7 Dec 2025]

https://oncodaily.com/voices/flatiron-health-422187

Context: Paradigm buys Flatiron’s clinical research unit and announces an oversubscribed $78M Series B.

Key point: Combined AI-enabled trial platform and Flatiron’s US community oncology network aim to run faster, more inclusive trials in community/rural settings.

Implication: Could shift oncology trial execution away from large academic hubs toward distributed real-world sites, impacting recruitment, diversity, and cost.

🧯 Ipilimumab + nivolumab in rare cancers after PD-1 exposure [6] [US • JCO OA 2025]

https://ascopubs.org/doi/10.1200/OA-25-00110

Context: S1609/DART basket trial of ipilimumab (1 mg/kg q6w) + nivolumab (240 mg q2w) in rare solid tumors; prior PD-1/L1 exposure allowed.

Key point: Clinical benefit rate was 26% both with and without prior PD-1/L1; multivariable HR for PFS 1.18 and OS 1.11 showed no significant differences.

Implication: Supports continued development and trial eligibility for anti–PD-1–pretreated patients receiving ipi/nivo combinations in rare malignancies.

🧫 FOLR1-CAR T cleared for R/R osteosarcoma [7] [US • 2025]

https://oncodaily.com/voices/soheil-meshinchi-420814

Context: Fred Hutch FOLR1-CART previously used in infants with CBF/GLIS AML now cleared by FDA for osteosarcoma.

Key point: Trial (NCT07227571) will enroll patients aged 1–75 with R/R osteosarcoma; strong preclinical activity in FOLR1-high models underpins expansion.

Implication: Positions FOLR1-directed CAR T as an emerging modality in solid tumors and may open a path to other FOLR1+ pediatric and adult cancers.

🧬 Chemo-free ponatinib + blinatumomab in Ph+ ALL (GIMEMA ALL2820) [8] [EU • ASH 2025]

https://www.targetedonc.com/view/chemo-free-ponatinib-blinatumomab-improves-survival-in-ph-all

Context: Phase 3, head-to-head ponatinib + blinatumomab vs imatinib + chemotherapy in adult Ph+ ALL.

Key point: CHR 94.3% vs 79.4%; EFS 90% vs 74%; OS 94% vs 77%, with fewer deaths and improved MRD responses in the chemo-free arm at 23.4-month follow-up.

Implication: Strongly supports a new chemotherapy-free, targeted-immunotherapy standard of care in frontline Ph+ ALL.

🛡️ Evorpacept + R2 in frontline indolent B-cell NHL [9] [US • 7 Dec 2025]

https://www.globenewswire.com/news-release/2025/12/07/3201128/0/en/ALX-Oncology-Announces-Positive-Results-from-Ongoing-Investigator-Sponsored-Phase-2-Trial-Evaluating-Evorpacept-in-Combination-with-Standard-of-Care-Treatment-in-Patients-with-Indo.html

Context: Phase 2 IST of CD47 blocker evorpacept + rituximab + lenalidomide in previously untreated indolent NHL (FL and MZL).

Key point: CR rate 92%, PR 8%, ORR 100%; 1-year PFS 91% and OS 100%, with a tolerable safety profile compared to historical R2 CR ~50%.

Implication: Reinforces CD47 blockade plus anti-CD20 as a potent chemotherapy-free strategy in iNHL and supports larger, registration-directed trials.

🌞 Lower-dose ipilimumab improves melanoma outcomes [10] [Sweden • 7 Dec 2025]

https://www.insideprecisionmedicine.com/topics/oncology/lower-immunotherapy-dose-boosts-response-by-30-in-melanoma-patients/

Context: Retrospective study (~400 advanced melanoma patients) comparing standard vs reduced-dose ipilimumab with nivolumab.

Key point: Response rate 49% vs 37%; median PFS 9 vs 3 months; OS 42 vs 14 months; grade ≥3 AEs 31% vs 51% favoring the lower-dose regimen.

Implication: Challenges conventional dosing assumptions and may drive optimization of ICI dose to improve efficacy, tolerability, and cost.

Why It Matters

Myeloma epigenetics & CD47/SIRPα in lymphoma: Gintemetostat and evorpacept signal continued diversification beyond BCMA in myeloma and CD20 in iNHL.
Chinese innovation goes global: The Takeda–Innovent partnership exemplifies how China-origin ADCs are being rapidly globalized via big-pharma alliances.
Screening & MRD infrastructure: Astrin’s Certitude and Natera–Foresight consolidate AI-proteomic early detection and ultra-sensitive MRD as core oncology platforms.
Trials closer to home: The Paradigm–Flatiron transaction may structurally shift oncology trial access toward community and rural centers using AI-enabled workflows.
Dose and sequence of IO: Data from S1609, low-dose ipilimumab, and ponatinib/blinatumomab highlight how prior PD-1 exposure and dosing strategy can be optimized without sacrificing benefit.

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FAQ

How strong is the evidence for gintemetostat in myeloma?

Early Phase 1 data show modest single-agent responses but clear disease control in a heavily pretreated, high-risk population, supporting further combination development [1].

What cancers are covered in the Takeda–Innovent ADC deal?

IBI363 and IBI343 are being developed for NSCLC, CRC, gastric, and pancreatic cancers, with Takeda holding rights outside Greater China and an option on IBI3001 [2].

How does Certitude compare to imaging?

Certitude offers 92% sensitivity, 93% specificity and very high NPV, particularly attractive as a supplemental test in women with dense breasts where mammography is less sensitive [3].

Why is PhasED-Seq important for Natera?

It adds extremely low LOD ctDNA MRD, enhancing performance in lymphoma and potentially enabling earlier relapse detection and MRD-driven trial designs [4].

Does prior PD-1 exposure preclude benefit from ipi/nivo?

In S1609/DART, prior PD-1/L1 exposure did not significantly affect CBR, PFS or OS, supporting inclusion of such patients in combination IO trials [6].

Is ponatinib + blinatumomab ready for routine Ph+ ALL use?

Phase 3 data show superior survival and MRD outcomes vs imatinib + chemotherapy, strongly positioning the regimen as a new standard pending broader guideline adoption [8].

Entities / Keywords

Gintemetostat; KTX-1001; MMSET; NSD2; triple-class refractory multiple myeloma.
Takeda; Innovent Biologics; IBI363; IBI343; IBI3001; CLDN18.2 ADC; PD-1/IL-2α-bias.
Astrin Biosciences; Certitude™ Breast; deep proteomics; AI-based screening.
Natera; Foresight Diagnostics; PhasED-Seq; MRD; ctDNA; lymphoma.
Paradigm Health; Flatiron Health; AI-enabled trials; community oncology.
Ipilimumab; nivolumab; S1609; DART; rare cancers; prior PD-1 exposure.
Fred Hutch; FOLR1-CART; osteosarcoma; NCT07227571.
Ponatinib; blinatumomab; Ph+ ALL; GIMEMA ALL2820.
ALX Oncology; evorpacept (ALX148); rituximab; lenalidomide; iNHL.
Nivolumab + ipilimumab dosing; advanced melanoma; Sweden; dose optimization.